CN113966229A

CN113966229A - Method for improving the quality of life of peanut allergic patients

Info

Publication number: CN113966229A
Application number: CN202080033786.0A
Authority: CN
Inventors: C·伯奇伍德
Original assignee: Aimu Therapy Co
Current assignee: Societe des Produits Nestle SA
Priority date: 2019-05-10
Filing date: 2020-05-08
Publication date: 2022-01-21
Also published as: EP3965815A1; US20200368304A1; US20230090380A1; EP3965815A4; CA3137295A1; JP2022532547A; US11229673B2; WO2020231843A1; AU2020276213A1

Abstract

The present disclosure relates to methods of improving the quality of life of peanut allergic subjects. In certain embodiments, the present disclosure provides methods of improving the quality of life of peanut allergic subjects by administering a peanut composition according to an oral immunotherapy plan. In certain embodiments, the present disclosure provides methods of improving the quality of life of a peanut allergic subject by informing the subject to whom they will be or are being administered a peanut composition according to an oral immunotherapy plan.

Description

Method for improving the quality of life of peanut allergic patients

Cross Reference to Related Applications

The present application claims priority benefits of U.S. provisional application No.62/846,481 filed on day 5/10 in 2019, U.S. provisional application No.62/855,384 filed on day 5/31 in 2019, and U.S. provisional application No.62/967,948 filed on day 1/30 in 2020; each of these U.S. provisional applications is incorporated herein by reference for all purposes.

Technical Field

Described herein are methods for improving the quality of life of peanut allergic patients.

Background

Peanut allergy is the allergy and hypersensitivity of the immune system to peanut proteins. Peanut allergies often occur in childhood and are usually life-long afflictions if there is no effective treatment. Allergic reactions to peanuts can be serious and life-threatening and are a major source of serious food-induced allergic reactions.

Peanut allergy imposes a huge burden on individuals and their caregivers/families. Management of peanut allergies involves ongoing medical care, financial costs, and care to avoid peanut or other compliance with medical recommendations. These burdens may manifest in a variety of ways, including anxiety symptoms and depression symptoms. Anxiety about the risk of allergic events can lead to exclusion of peanut allergic children from social events, and the like. See, for example, Bollinger et al, The impact of food Allergy on The day activities of children and The family simulations, Ann, Allergy elevation Immunol, Vol.96, p.415, 421, 2006. In summary, these burdens may affect the quality of life (QoL) of an individual, and even the quality of life of its caregivers or family members. See, for example, King et al, Impact of tiny Allergy on quality of life, stress and inertia in the family, Allergy, Vol.64, No. 3, page 461-. The burden on peanut allergic individuals may be greater than that experienced by individuals with other severe chronic diseases, including type 1 diabetes. See, for example, Avery et al, Assessment of quality of life in children with peak allowances, ped.

Standards of care for the treatment of peanut allergy generally include dietary elimination and avoidance of peanuts, education for signs of allergic reactions, and administration of injectable epinephrine to respond to severe allergic reactions caused by dietary exposure to peanut proteins. However, accidental ingestion of peanuts is common due to the difficulty in interpreting the presence of unreported ingredients in food labels and unlabeled foods. Oral Immunotherapy (OIT) is a promising new treatment for peanut allergy. See, e.g., Bird et al, effectiveness and Safety of AR101 in Oral Immunotherapy for Peanout Allergy of solutions of ARC 001; a random Double-blunt, plant-Controlled Phase 2Clinical Trial, J.Clin.Immunol.Pract, Vol.6, 2 nd, 476 th and 485 th pages, 2018. Peanut OIT involves exposing patients to increasing doses of peanut protein to induce desensitization, which is intended to reduce the risk of a severe response when exposed to peanuts accidentally.

Disclosure of Invention

Described herein are methods of improving the quality of life of peanut allergic patients by oral immunotherapy according to an oral immunotherapy plan.

In some embodiments, a method of improving the quality of life of a peanut allergic patient comprises: the peanut composition is administered to the patient according to an oral immunotherapy plan.

In some embodiments, the patient is informed that the peanut composition is being administered. In some embodiments, the patient is informed that the peanut composition is being administered to the patient at the beginning of the oral immunotherapy plan. In some embodiments, the patient is informed that the peanut composition is being administered to the patient during the dosing phase of the oral immunotherapy plan. In some embodiments, the patient is informed that the peanut composition is being administered to the patient during the maintenance phase of the oral immunotherapy plan.

In some embodiments, the method further comprises informing the patient that the peanut composition is being administered to the patient. In some embodiments, the patient is informed that the peanut composition is being administered to the patient prior to the start of the oral immunotherapy plan. In some embodiments, the patient is informed that the peanut composition is being administered to the patient during the dosing phase of the oral immunotherapy plan. In some embodiments, the patient is informed that the peanut composition is being administered to the patient during the maintenance phase of the oral immunotherapy plan.

In some embodiments, quality of life questionnaires (qolqs) are used to measure quality of life improvements. In some embodiments, the QoLQ comprises one or more scored measurement domains. In some embodiments, the QoLQ is a Food Allergy Quality of Life Questionnaire (FAQLQ). In some embodiments, the FAQLQ is FAQLQ-childhood table (FAQLQ-CF), FAQLQ-junior-year table (FAQLQ-TF), FAQLQ-adult table (FAQLQ-AF), or FAQLQ-father-mother table (FAQLQ-PF).

In some embodiments, a method of improving the quality of life of a peanut allergic patient, as assessed by the quality of life questionnaire (QoLQ), comprises administering a peanut composition to the patient according to an oral immunotherapy plan. In some embodiments, the patient is informed that the peanut composition is being administered. In some embodiments, the patient is informed that the peanut composition is being administered to the patient at the beginning of the oral immunotherapy plan. In some embodiments, the patient is informed that the peanut composition is being administered to the patient during the dosing phase of the oral immunotherapy plan. In some embodiments, the patient is informed that the peanut composition is being administered during the maintenance phase of the oral immunotherapy plan. In some embodiments, the method further comprises informing the patient that the peanut composition is being administered to the patient. In some embodiments, the method further comprises informing the patient that the peanut composition is being administered to the patient, and informing the patient that the peanut composition is being administered to the patient prior to starting the oral immunotherapy plan. In some embodiments, the method further comprises informing the patient that the peanut composition is being administered to the patient, and informing the patient that the peanut composition is being administered to the patient during a dosing phase of the oral immunotherapy plan. In some embodiments, the method further comprises informing the patient that the peanut composition is being administered to the patient, and informing the patient that the peanut composition is being administered to the patient during a maintenance phase of the oral immunotherapy plan. In some embodiments, the QoLQ comprises one or more scored measurement domains. In some embodiments, the QoLQ is a Food Allergy Quality of Life Questionnaire (FAQLQ). In some embodiments, the FAQLQ is FAQLQ-childhood table (FAQLQ-CF), FAQLQ-junior-year table (FAQLQ-TF), FAQLQ-adult table (FAQLQ-AF), or FAQLQ-father-mother table (FAQLQ-PF). In some embodiments, QoLQ is a Food Allergy Independent Measure (FAIM). In some embodiments, the FAIM is a FAIM-childhood table (FAIM-CF), a FAIM-minor-year table (FAIM-TF), a FAIM-adult table (FAIM-AF), or a FAIM-father-mother table (FAIM-PF). In some embodiments, the QoLQ is a pediatric quality of life manifest (PedsQL).

In some embodiments of the foregoing methods, the quality of life is improved for at least 6 months. In some embodiments, the quality of life is improved for at least 12 months.

In some embodiments, the one or more score fields of QoLQ each score on a scale between 1 and 7, or each convert to a score between a first score and a second score, wherein the second score indicates poor quality of life. In some embodiments, the quality of life of the patient is at least a 0.5 point improvement in one or more domains of QoLQ at a second time point after the period of oral immunotherapy as compared to the assessment at the first time point before the period of oral immunotherapy. In some embodiments, the patient's quality of life is at least a 0.5 point improvement in the total score of QoLQ at a second time point after the period of oral immunotherapy as compared to the assessment at the first time point prior to the period of oral immunotherapy; where the total score is the average of the scores for each domain. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point is the dosing phase of the oral immunotherapy plan. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least 1 month of the maintenance therapy for which the oral immunotherapy is planned.

In some embodiments, quality of life questionnaires (qolqs) are used to measure quality of life improvements. In some embodiments, QoLQ is a Food Allergy Independent Measure (FAIM). In some embodiments, the FAIM is a FAIM-childhood table (FAIM-CF), a FAIM-minor-year table (FAIM-TF), a FAIM-adult table (FAIM-AF), or a FAIM-father-mother table (FAIM-PF). In some embodiments, the patient's quality of life is at least a 0.5 point improvement in the total score of QoLQ at a second time point after the period of oral immunotherapy as compared to the assessment at the first time point prior to the period of oral immunotherapy; where the total score is the average of the scores for each domain. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point is the dosing phase of the oral immunotherapy plan. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least 1 month of the maintenance therapy for which the oral immunotherapy is planned.

In some embodiments, the quality of life improves after 6 months of the oral immunotherapy plan.

In some embodiments, the oral immunotherapy plan includes a dosing phase and a maintenance phase. In some embodiments, the peanut composition is administered to the patient daily during the maintenance phase. In some embodiments, the maintenance phase is at least 3 months. In some embodiments, the peanut composition is administered to the patient at a dose of about 300mg peanut protein or more during the maintenance phase of the oral immunotherapy plan. In some embodiments, the medicated phase comprises administering to the patient two or more different doses between about 3mg and the dose of the about initial maintenance phase dose.

In some embodiments, the oral immunotherapy plan includes a dosing phase between about 3 months and about 2 years in length.

In some embodiments, the oral immunotherapy plan further comprises an initial escalation phase.

In some embodiments, the patient is about 4 years old or older. In some embodiments, the patient is between about 4 years of age and about 17 years of age. In some embodiments, the patient is between about 8 and about 17 years of age.

In some embodiments, the method comprises measuring the quality of life prior to administering the peanut composition to the patient according to an oral immunotherapy plan. In some embodiments, the method comprises measuring the quality of life after administering the peanut composition to the patient according to an oral immunotherapy plan. In some embodiments, the method comprises measuring the quality of life after informing the patient that the peanut composition is being administered. In some embodiments, the quality of life of the patient is improved as determined by a quality of life questionnaire (QoLQ).

Drawings

Figure 1 shows self-reported quality of life results for subjects (age 8 to 17 years) participating in two peanut OIT clinical trials (PALISADE trial and open label extension of the PALISADE trial) at three time points (left: FAQLQ; right: FAIM) as measured by a food allergy quality of life questionnaire (FAQLQ; e.g., FAQLQ-CF or FAQLQ-TF) and by a food allergy independent measure (FAIM; e.g., FAIM-CF or FAIM-TF). The first time point occurs during the screening of the first clinical trial (PALISADE). The second time point (T2) occurred after completion of the double-blind placebo-controlled food challenge (DBPCFC) performed at PALISADE exit and before the start of open label expansion. The third point in time (T3) occurs at the exit of the open label extension. The left panel of figure 1 shows the FAQLQ total score and the mean score of the domains of allergen avoidance and dietary restriction, risk of accidental exposure and emotional impact (indicating 95% confidence intervals). The right graph of fig. 1 shows the average score (indicating 95% confidence intervals) for the FAIM total score and the issues of product avoidance and social impact on the expectation of the results. Four of the total score results and six domain/question score results each exceeded the threshold of 0.5 for the minimum clinically significant difference (MCID) between the PALISADE screen and T3, and are indicated by an asterisk above the bar.

Figure 2 shows quality of life results reported by proxies participating in two peanut OIT clinical trials (PALISADE and open label extension of PALISADE) at three time points (left: FAQLQ; right: FAIM) as measured by a food allergy quality of life questionnaire (FAQLQ; e.g., FAQLQ-PF) and by a food allergy independent measure (FAIM; e.g., FAIM-PF) on subjects (age 4 to 17 years). The first time point occurs during the screening of the first clinical trial (PALISADE). The second time point (T2) occurred after completion of the double-blind placebo-controlled food challenge (DBPCFC) performed at PALISADE exit and before the start of open label expansion. The third point in time (T3) occurs at the exit of the open label extension. The left graph of fig. 2 shows the FAQLQ total score and the average scores for domains of mood impact, food anxiety and social and dietary restrictions (indicating 95% confidence intervals). The right graph of fig. 2 shows the FAIM child's expectation of the results (by the attorney) and the average score of the parent/caregiver's expectation of the results (indicating a 95% confidence interval). Parents or caregivers of children aged 13 to 17 years were not tested for this question with respect to the child's expectation of the results (by proxy). The question that the parent/caregiver expects for a result exceeds the minimum clinically significant difference (MCID) between PALISADE screening and T3, and is indicated by an asterisk above the bar.

Figure 3 shows the change in quality of life for various subjects from the screening of the first peanut OIT clinical trial (palsad) to the exit of the open label extension of palsad, including the time points between palsad and open label extension. The dots indicate the mean (indicating 95% confidence intervals) change in the total score of the Food Allergy Quality of Life Questionnaire (FAQLQ) by self-reporting (e.g., FAQLQ-CF or FAQLQ-TF) or by agent reporting (e.g., FAQLQ-PF). Triangle points indicate mean (indicating 95% confidence intervals) changes in the total Food Allergy Independent Measurement (FAIM) score by self-reporting (e.g., FAIM-CF or FAIM-TF) or by surrogate reporting (e.g., FAIM-PF). The solid and dashed lines indicate "yes" and "no," respectively, and relate to whether a particular subject tolerates at least 600mg of peanut protein at the time point between clinical trials (i.e., PALISADE exit), as measured in a double-blind placebo-controlled food challenge, whether the subject experienced a systemic anaphylaxis during the first clinical trial (PALISADE) or open label extension, and whether the subject reported the use of epinephrine during the first clinical trial (PALISADE) or open label extension. The vertical dashed line (+/-0.5 score change) indicates the minimum clinically significant difference (MCID) for each QoL tool.

Figure 4 shows FAQLQ and FAQLQ total and domain scores reported by participants aged 8 to 12 years in a european clinical trial of AR101 at active group screening (first row per total or domain score), active group withdrawal (second row per total or domain score), placebo group screening (third row per total or domain score), and placebo group withdrawal (fourth row per total or domain score).

Figure 5 shows FAQLQ and FAQLQ total and domain scores reported by participants aged 13 to 17 years in european clinical trials of AR101 at active group screening (first row per total or domain score), active group withdrawal (second row per total or domain score), placebo group screening (third row per total or domain score), and placebo group withdrawal (fourth row per total or domain score).

Fig. 6 shows the FAIM scores reported by the agents of the various domains reported by caregivers of participants aged 4 to 12 years in european clinical trials of AR101 at active group screening (first row of each domain), active group withdrawal (second row of each domain), placebo screening (third row of each domain), and placebo withdrawal (fourth row of each domain).

Detailed Description

Described herein are methods of improving the quality of life of peanut allergic patients. The method can include administering a peanut composition to a patient according to an oral immunotherapy plan. It has been found that subjects suffering from reduced quality of life due to peanut allergy may have an improved quality of life by being treated with a peanut composition according to an oral immunotherapy plan. In multiple large-scale clinical trials testing the efficacy of investigational peanut protein oral biopharmaceutical AR101 in oral immunotherapy, significant improvements in the quality of life reported by the subjects and reported by the agents of each of the activity cohorts were observed after the initial desensitization and maintenance therapy periods. These substantial improvements throughout the cohort indicate that individuals receiving the treatment described herein may have an improvement in quality of life.

The quality of life of a subject can be improved by informing the subject that they will or are administering a peanut composition according to an oral immunotherapy plan for treating peanut allergy. In contrast to administering the composition in blind studies without knowledge of treatment, knowledge of treatment with the active therapeutic agent (i.e., peanut composition) can lead to an improvement in quality of life. Oral immunotherapy involves administering peanut proteins by the same route that occurs with accidental dietary exposure (i.e., oral ingestion). Once desensitization is achieved, oral immunotherapy can therefore provide the patient and/or their caregiver with additional certainty of protecting the patient from accidental exposure to peanut proteins as compared to other immunotherapy approaches, such as those based on skin exposure or injection. This effect may be independent of the actual desensitization. After informing the patient that a peanut composition is being administered, each dose of peanut protein according to an oral immunotherapy plan can enhance the patient's confidence in desensitization to their accidental exposure and thus improve the patient's quality of life over time. Thus, the methods of improving a patient's quality of life described herein can include administering a peanut composition to a treatment-conscious patient (i.e., informed that they are receiving a peanut composition rather than a placebo). The patient may be informed of the active treatment prior to starting the oral immunotherapy plan or during the oral immunotherapy plan, such as during a dosing phase or a maintenance phase of the oral immunotherapy plan. In some embodiments, the method comprises informing the patient of the active treatment (i.e., the peanut composition is being administered to the patient).

Oral Immunotherapy (OIT) is a method of inducing desensitization of a subject to an allergen by periodically exposing the subject to increasing doses of the allergen. For peanut allergy, the regimen for OIT typically involves a dosing phase (also known as an accumulation phase) and a maintenance phase. OIT may also include an initial escalation phase, although this phase is optional and not necessary for treatment. The initial escalation phase involves exposure to a small dose of peanut protein under clinical supervision to determine the sensitivity of the patient to peanut protein. This initial incremental phase typically occurs over the course of several (e.g., three or more) hours to two days. These small doses are increased until the subject reaches the target dose or the highest tolerated dose for the initial escalation phase. The subject then typically begins the dosing phase, starting with the highest tolerated dose or slightly lower dose administered in the initial escalation phase, and progressing through a series of dose escalations in the dosing phase. In addition, peanut OIT includes a maintenance phase involving continuous application of peanut protein for a period of time. One goal of oral immunotherapy is to establish a desensitized state in which the treated subject is less likely to suffer a severe or life-threatening allergic reaction upon accidental exposure to peanut protein.

Peanut allergic subjects may suffer from reduced quality of life, and their quality of life may be improved by the methods described herein.

Definition of

As used herein, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.

Reference herein to "about" a value or parameter includes (and describes) variations that relate to that value or parameter itself. For example, a description referring to "about X" includes a description of "X".

The term "desensitization" is used herein to refer to oral immunotherapy as a food allergen to which the subject's threshold of response is increased. Desensitization to food allergens can be tested using methods known in the art, including oral food challenge. Desensitization can be partial, wherein the subject tolerates increased amounts of food allergens compared to before treatment, but still responds to higher doses of food allergens; or desensitization may be complete, wherein the patient tolerates all tested doses of food allergen.

As used herein, the phrase "quality of life" is synonymous with "disease-related quality of life" and "health-related quality of life" and refers to the portion of a subject's life that is affected by a food allergy and/or that is affected by treatment thereof.

Unless otherwise indicated, the terms "effective," "efficacy," or "effectiveness" are used herein to refer to the ability of a therapy to induce immune modulation (such as desensitization) or to maintain a desired immune state (such as a desensitized state).

As used herein, the "maintenance phase" refers to the phase of peanut protein oral immunotherapy that includes administration of peanut protein to a patient (i.e., a maintenance dose), and occurs after the dosing phase is complete.

As used herein, "mild allergic adverse event" refers to an OIT treatment-related allergic adverse event that is observed or experienced that is associated with brief discomfort but does not require immediate medical intervention (such as hospitalization or epinephrine) and does not substantially interfere with daily activities.

As used herein, "moderate allergic adverse event" refers to an observed or experienced allergic adverse event associated with discomfort to a sufficient extent to interfere with daily activities and may be suggestive of a medical intervention and/or additional observed OIT treatment-related allergic adverse events.

As used herein, "daily" administration refers to the administration of one dose per consecutive calendar day. The dose may be administered as a single portion on a calendar day, or subdivided into multiple portions administered within the same calendar day.

As used herein, the phrase "severe allergic adverse event" refers to an allergic adverse event observed or experienced in connection with OIT treatment resulting in an allergy requiring hospitalization and/or administration of epinephrine or other life-saving medical intervention.

The term "subject" or "patient" is used synonymously and interchangeably herein to describe a human of any age.

A subject "tolerates" a dose when it is administered to the subject without any moderate or severe allergic adverse events. The subject is considered to tolerate this dose even if mild allergic adverse events are observed or experienced.

The terms "treating", "treating" and "treatment" are used synonymously herein to refer to any act that provides a benefit to a subject suffering from a disease state or disorder, including ameliorating the disorder by: alleviating, inhibiting, suppressing, or eliminating at least one symptom; delay the progression of the disease; delay the recurrence of the disease; inhibition of disease; or partially or completely reduce the response or reaction to the allergen.

By "dosing phase" is meant a phase of oral immunotherapy characterized by a series of increasing food allergen doses, starting with administration of a food allergen dose that is lower than the highest dose administered to the patient during oral immunotherapy, and ending when the highest dose administered to the patient during oral immunotherapy is reached.

It should be understood that aspects and variations of the invention described herein include aspects and variations that "consist of and/or" consist essentially of.

When a range of values is provided, it is understood that each intervening value, to the extent that there is no such stated, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the scope of the disclosure. Where the stated range includes an upper limit or a lower limit, ranges excluding any of those included limits are also included in the disclosure.

The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. This description is provided to enable one of ordinary skill in the art to make and use the invention and is provided in the context of a patent application and its requirements. Various modifications to the described embodiments will be readily apparent to those skilled in the art, and the generic principles herein may be applied to other embodiments. Thus, the present invention is not intended to be limited to the embodiments shown, but is to be accorded the widest scope consistent with the principles and features described herein.

The disclosures of all publications, patents and patent applications mentioned herein are hereby incorporated by reference in their entirety. To the extent any reference incorporated by reference conflicts with the present disclosure, the present disclosure shall control.

Method for improving quality of life

The quality of life of peanut allergic patients can be improved by administering a peanut composition to the patient according to an oral immunotherapy plan. In some embodiments, the quality of life of peanut allergic patients can be improved by informing the patients that they are administering or will be administering a peanut composition according to an oral immunotherapy plan. In some embodiments, the quality of life of peanut allergic patients can be improved by instructing the caregiver of the patient to inform the patient that they are administering or will be administering a peanut composition according to an oral immunotherapy plan.

At any time prior to or during oral immunotherapy, the subject may be informed that they will or are administering the peanut composition according to an oral immunotherapy schedule, or the subject's caregiver may be informed that the subject will or is administering the peanut composition according to an oral immunotherapy schedule. In some embodiments, the subject is informed, or a caregiver to the subject is instructed to inform the subject, prior to starting the oral immunotherapy plan. In some embodiments, the subject is informed, or a caregiver to the subject is instructed to inform the subject, prior to initiating the dosing phase of the oral immunotherapy plan. In some embodiments, the subject is informed during the dosing phase of an oral immunotherapy plan, or a caregiver to the subject is instructed to inform the subject. In some embodiments, the subject is informed after the dosing phase of the oral immunotherapy plan, or a caregiver to the subject is instructed to inform the subject. In some embodiments, the subject is informed during the maintenance phase of the oral immunotherapy plan, or a caregiver to the subject is instructed to inform the subject. In some embodiments, the subject is informed after at least one month of maintenance therapy planned for oral immunotherapy (such as at least 2 months, at least 3 months, at least 6 months, and at least 12 months of maintenance therapy for oral immunotherapy), or a caregiver to the subject is instructed to inform the subject.

The subject may undergo a quality of life assessment before, during or after oral immunotherapy. Peanut allergy affects quality of life through allergic reactions to peanut proteins. However, even in the absence of an allergic reaction, peanut allergic subjects suffer from an impairment in quality of life, including fear of allergic reactions, financial burden of allergy, social limitations of allergy, and the like. The subject and its caregivers must devote a great deal of time to review and validate food choices, such as by reading food labels, interrogating ingredients in unlabeled foods, or avoiding preparing foods in environments with potential cross-contamination. The subject and its caregivers may experience anxiety in these burdens, which may further manifest as depressive symptoms. The subject may avoid living alone or even eating alone because of concerns about the rapid development of allergic reactions. These effects together reduce the quality of life of the subject.

Methods of measuring quality of life (such as disease-related QoL) before, during, or after OIT have been developed and validated for measuring quality of life in food allergy (such as peanut allergy) subjects. The most common method of assessing quality of life employs questionnaires designed to assess qualitatively and/or quantitatively the burden of food allergies, such as peanut allergy, in one or more domains, each domain having one or more problems. Exemplary questionnaires are generally (1) effective, meaning that part of the quality of life being measured is related to food allergies; (2) reproducible, meaning that questionnaires taken under similar conditions are equivalent and can generally produce similar results without a change in food allergy burden or treatment burden; (3) in response, this means that a change in food allergy burden and/or treatment burden is detected and/or detectable; and (4) interpretable, meaning that the change in score is clinically significant, as determined by the smallest clinically significant difference in questionnaires (MCID).

An improvement in the quality of life of a subject involves a change between at least two time points. Furthermore, the improvement is understood with respect to a specific tool (such as a specific quality of life questionnaire or other QoL assessment). For example, if an individual's quality of life is assessed by a quality of life questionnaire, an improvement is an improvement in the score of that same quality of life questionnaire, such as an improvement in a particular domain or an improvement in the overall score of the questionnaire. In some embodiments, the improvement is clinically significant, such as equal to or greater than the minimal clinically significant difference in questionnaires (MCID). In some embodiments, the improvement is a change in a domain score or total score of a quality of life questionnaire between one time point (such as a baseline measurement) and a second time point.

In some embodiments, a skilled medical provider (such as a physician, nurse, allergy specialist, or other professional trained in the art of allergy treatment) may select a QoL assessment tool suitable for subjects who will be or are being treated for food allergy (such as peanut allergy) by oral immunotherapy. Preferably, the QoL assessment tool is age-appropriate and validated against a particular age range of the subject. For younger subjects, for example for subjects below 12 years of age, a surrogate report may be required (such as a report completed by the subject's caregiver about the subject's peanut allergy) or may supplement a self-report. For

subjects

6, 7, or over 8 years old, self-reporting alone may be sufficient, but not always. In some embodiments, the assessment tool may be validated against the subject's native language (for self-reporting) and/or the subject's caregiver (for agent reporting). In some embodiments, the assessment tool can perform cultural verification, for example, verification in a country or region in which the subject (for self-reporting) and/or the subject's caregiver (for agent reporting) reside.

In some embodiments, quality of life may be assessed by a quality of life questionnaire (QoLQ), such as QoLQ specific to food allergies. In some embodiments, the QoLQ specific for a food allergy is a QoLQ specific for a peanut allergy. QoS is typically divided into one or more domains, where each domain relates to a category of physical, psychological, emotional, or social function or well-being. The domain of QoS may include one or more issues. The QoLQ may score one or more domains and/or one or more questions individually and/or collectively. Exemplary domains and/or issues covered may include, but are not limited to: overlooking, teasing, family events, school events, social events, field trips, parties, lodging parties, playing at a friend's home, time for preparing food, physical state, mental state, emotional state, desire for outcome, perceived risk, parental anxiety, parental depression, psychosocial effects, parental reactions, family support, social prevention, food allergen identification, mood effects, food-related anxiety, social restrictions, allergen avoidance, dietary restrictions, risk of accidental exposure, fear, perception, independence and/or the burden of carrying epinephrine. In some embodiments, the domains and/or questions measured by QoLQ include any domains and/or questions validated as being related to food allergies and/or the burden of treating food allergies. In some embodiments, the domains and/or questions measured by QoLQ include any domains and/or questions validated as being related to food allergy (i.e., peanut allergy) and/or the burden of treating food allergy (i.e., peanut allergy).

In some embodiments, the quality of life of a peanut allergic subject can be assessed by administering one or more qolqs to the peanut allergic subject to measure the quality of life of the subject. In some embodiments, the quality of life of a peanut allergic subject can be assessed by an agent by administering one or more qolqs to a caregiver of the subject to measure the quality of life of the subject. In some embodiments, the quality of life of a peanut allergic subject can be assessed by administering one or more qolqs to the peanut allergic subject and by administering one or more qolqs to a caregiver of the subject to measure the quality of life of the subject. In some embodiments, the caregiver of the subject is any individual who is aware of the physiological, emotional, financial, and/or physical burden of a peanut allergy on the subject. In some embodiments, the caregiver of the subject is a family member (such as a parent, grandparent, sibling, aunt, uncle, paternity, etc.) or other guardian (such as a legally assigned guardian).

In some embodiments, the quality of life of a peanut allergic subject can be assessed by administering one or more qolqs to measure the quality of life of the subject. In some embodiments, the one or more qolqs for measuring quality of life of a subject comprise one or more qolqs selected from: food allergy quality of life-parental burden questionnaire (FAQL-PB), Food Allergy Impact Scale (FAIS), Food Allergy Independent Measurements (FAIM), food allergy independent measurements pediatric watch (FAIM-CF), food allergy independent measurements juvenile questionnaire (FAIM-TF), food allergy independent measurements adult watch (FAIM-AF), food allergy independent measurements father watch (FAIM-PF), Food Allergy Parental Questionnaire (FAPQ), child health questionnaire father watch (CHQ-PF), parent food allergy self-efficacy scale (FASE-P), pediatric allergy disease quality of life questionnaire (paddlq), food allergy quality of life questionnaire-father watch (FAQLQ-PF), food allergy quality of life questionnaire-pediatric watch (FAQLQ-CF), food allergy quality of life questionnaire-few year watch (FAQLQ-TF), A food allergy quality of life assessment tool for adolescents (FAQL-tene), your and your food allergy questionnaire, food allergy quality of life questionnaire-adult table (FAQLQ-AF), 36 short-form health survey (SF-36), EuroQol EQ-5D (such as EuroQol 5D youth (EQ-5D-Y) or grade 5 EQ-5D (EQ-5D-5L), Hospital Anxiety and Depression Scale (HADS), allergy-influencing mood and life to peanut (APPEAL) survey and pediatric quality of life checklist (PedsQL). In some embodiments, the one or more QoLQs comprise FAQLQQs, such as FAQLQ-CF, FAQLQ-TF, FAQLQ-AF or FAQLQ-PF. in some embodiments, the one or more FAQLQLQLQLQs comprise FAQLQ-CF, FAQLQ-AF reported from QLQ-CF, FAQLQ-AF, the one or more qolqs include FAQLQ-PF reported by the agent. In some embodiments, the one or more qolqs comprise self-reported FAQLQ-CF, FAQLQ-TF, FAQLQ-AF, and agent-reported FAQLQ-PF. In some embodiments, the one or more qolqs comprise a FAIM, such as FAIM-CF, FAIM-TF, FAIM-AF, or FAIM-PF.

QoLQ generally includes one or more score domains, where each domain reflects an aspect or category related to the quality of life of the subject. In some embodiments, QoLQ will assign a numerical score to each domain along the scale. The scores may be on any scale, with a first score associated with better quality of life and a second score associated with poorer quality of life. For example, the scale may be between 1 and 5, between 1 and 6, between 1 and 7, or any other selected value. According to some scales, a higher score may be used to indicate a poorer quality of life. The overall score, cumulative score, and/or multi-domain score may also be evaluated based on an average score of multiple domains of QoLQ. In some embodiments, the domain score and/or the total score of QoLQ may be converted to a universal scale, e.g., a score between 1 and 7, where 7 is associated with poor quality of life, or a score between a first score and a second score, where the second score is associated with poor quality of life.

The QoLQ administered should be appropriate for the subject and/or their caregiver. In some embodiments, the one or more qolqs administered are translated into a language understood by the subject and/or their caregiver. In some embodiments, the administered QoLQ or qolqs are validated to ensure language and cultural applicability to the subject and/or their caregiver.

In some embodiments, the quality of life of the subject is assessed, at least in part, by the agent by administering the QoLQ for the subject to a caregiver of the subject. In some embodiments, a QoLQ administered to a caregiver of a subject to assess QoL of the subject is a QoLQ designed for surrogate assessment of food allergic (such as peanut allergic) subjects. In a non-limiting exemplary embodiment, the QoLQ administered to the caregiver of the subject to assess the QoL of the subject by the agent is FAQLQ-PF.

The quality of life of a peanut allergic subject can be improved by administering a peanut composition to the subject according to an oral immunotherapy plan and/or informing the subject that they will be or are being administered a peanut composition according to an oral immunotherapy plan. As the subject continues to administer (and/or realizes that they will continue to administer) the peanut composition according to the oral immunotherapy plan, the improvement in the quality of life of the subject may persist for a period of time after improvement (including continuing to further improve). Even if the subject's physiological sensitivity to peanut proteins is not further improved, the improvement can persist, including continuing to improve. Thus, in some embodiments, the quality of life of the subject is improved by at least any one of about 1 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months, 48 months, or 60 months. In some embodiments, when the administration of the peanut composition to the subject is continued according to an oral immunotherapy plan, the quality of life of the subject is improved by at least any one of about 1 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months, 48 months, or 60 months. In some embodiments, the quality of life of the subject improves by at least any one of about 1 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months, 48 months, or 60 months after the subject has achieved peak desensitization to peanut proteins (such as measured by oral food challenge).

In some embodiments, the quality of life of a peanut allergic subject is improved by administering a peanut composition to the subject according to an oral immunotherapy plan and/or informing the subject that they will be administering or are administering a peanut composition according to an oral immunotherapy plan. In some embodiments, the improvement in quality of life is determined by improvement in one or more domains of one or more qolqs, where each domain is scored. In some embodiments, the score for each domain is converted to a score between the first score and the second score, wherein the second score indicates poor quality of life. In some embodiments, quality of life is assessed at a first time point and a second time point. In some embodiments, the improvement in quality of life of the subject between the first time point and the second time point is at least a minimal clinically significant difference. In some embodiments, the first time point is prior to oral immunotherapy. In some embodiments, the first time point is prior to a dosing phase of the oral immunotherapy. In some embodiments, the first time point is during a dosing phase of the oral immunotherapy. In some embodiments, the first time point is during a maintenance phase of oral immunotherapy. In some embodiments, the subject is informed that they will be administered a peanut composition according to an oral immunotherapy plan prior to the first time point. In some embodiments, the subject is informed that they will be administered a peanut composition according to an oral immunotherapy plan at a first time point. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point comprises a dosing phase of an oral immunotherapy plan. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the improvement in quality of life is determined by improvement in one or more domains of one or more qolqs, where each domain is scored. In some embodiments, at least one domain is a measure of anxiety. In some embodiments, the at least one domain is a measure of emotional impact, such as emotional impact on allergy and/or emotional impact on treatment of allergy. In some embodiments, at least one domain is a measure of social influence, such as limits of social interaction and/or participation. In some embodiments, at least one area is a measure of dietary impact, such as caloric intake, dietary diversity, and/or dietary rejection. In some embodiments, at least one field is a measure of anticipation, such as an expectation of treatment success and/or an expectation of future incidence of allergic reactions and/or an expectation of improvement in a disease condition. In some embodiments, the score for each domain is converted to a score between the first score and the second score, wherein the second score indicates poor quality of life. In some embodiments, quality of life is assessed at a first time point and a second time point. In some embodiments, the score at the first time point is equal to or greater than the midpoint of the scale. For example, in an exemplary embodiment, each domain scores on a scale of 1 to 7, where 7 indicates poor quality of life, and the score for one or more domains at a first point in time is equal to or greater than the midpoint of the scale, which is equal to or greater than 4. In some embodiments, the score of the one or more domains at the second point in time is less than the midpoint of the scale. For example, in an exemplary embodiment, each domain scores on a scale of 1 to 7, where 7 indicates poor quality of life, and the score of one or more domains at the second point in time is less than the midpoint of the scale, which is less than 4. In some embodiments, the first time point is prior to oral immunotherapy. In some embodiments, the first time point is prior to a dosing phase of the oral immunotherapy. In some embodiments, the first time point is during a dosing phase of the oral immunotherapy. In some embodiments, the first time point is during a maintenance phase of oral immunotherapy. In some embodiments, the subject is informed that they will be administered a peanut composition according to an oral immunotherapy plan prior to the first time point. In some embodiments, the subject is informed that they will be administered a peanut composition according to an oral immunotherapy plan at a first time point. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point comprises a dosing phase of an oral immunotherapy plan. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is improved by administering a peanut composition to the subject according to an oral immunotherapy plan and/or informing the subject that they will be administering or are administering a peanut composition according to an oral immunotherapy plan. In some embodiments, the improvement in quality of life is determined by an improvement in a total score of the one or more qolqs, wherein the total score is an average of the one or more domains of qolqs. In some embodiments, the total score is converted to a score between the first score and a second score, wherein the second score indicates poor quality of life. In some embodiments, quality of life is assessed at a first time point and a second time point. In some embodiments, the improvement in quality of life of the subject between the first time point and the second time point is at least a minimal clinically significant difference. In some embodiments, the first time point is prior to oral immunotherapy. In some embodiments, the first time point is prior to a dosing phase of the oral immunotherapy. In some embodiments, the first time point is during a dosing phase of the oral immunotherapy. In some embodiments, the first time point is during a maintenance phase of oral immunotherapy. In some embodiments, the subject is informed that they will be administered a peanut composition according to an oral immunotherapy plan prior to the first time point. In some embodiments, the subject is informed that they will be administered a peanut composition according to an oral immunotherapy plan at a first time point. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point comprises a dosing phase of an oral immunotherapy plan. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the improvement in quality of life is determined by an improvement in a total score of the one or more qolqs, wherein the total score is an average of the one or more domains of qolqs. In some embodiments, the total score is converted to a score between the first score and a second score, wherein the second score indicates poor quality of life. In some embodiments, quality of life is assessed at a first time point and a second time point. In some embodiments, the score at the first time point is equal to or greater than the midpoint of the scale. For example, in an exemplary embodiment, the total score scores on a scale of 1 to 7, where 7 indicates poor quality of life, and the total score at the first point in time is equal to or greater than the midpoint of the scale, which is equal to or greater than 4. In some embodiments, the total score at the second time point is less than the midpoint of the scale. For example, in an exemplary embodiment, each domain scores on a scale of 1 to 7, where 7 indicates poor quality of life, and the score of one or more domains at the second point in time is less than the midpoint of the scale, which is less than 4. In some embodiments, the first time point is prior to oral immunotherapy. In some embodiments, the first time point is prior to a dosing phase of the oral immunotherapy. In some embodiments, the first time point is during a dosing phase of the oral immunotherapy. In some embodiments, the first time point is during a maintenance phase of oral immunotherapy. In some embodiments, the subject is informed that they will be administered a peanut composition according to an oral immunotherapy plan prior to the first time point. In some embodiments, the subject is informed that they will be administered a peanut composition according to an oral immunotherapy plan at a first time point. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point comprises a dosing phase of an oral immunotherapy plan. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is FAQLQ-CF. In some embodiments, the total score of FAQLQ-CF administered to a peanut allergic subject at a first time point prior to or during the dosing phase of oral immunotherapy is 4 or higher. In some embodiments, at a first time point prior to or during the dosing phase of oral immunotherapy, the one or more domains of FAQLQ-CF administered to peanut allergic subjects score 4 or higher, such as in the allergen avoidance and diet restriction domains, score 4 or higher in the mood influencing domain, and/or score 4 or higher in the accidental exposure risk domain. In some embodiments, there is an improvement of at least 0.5 points, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of FAQLQ-CF administered to the subject after a second time point after the period of oral immunotherapy as compared to the total score of FAQLQ-CF administered to a peanut allergic subject at a first time point prior to oral immunotherapy. In some embodiments, there is at least a 0.5 point improvement, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of FAQLQ-CF administered to the subject at a second time point after the period of oral immunotherapy as compared to the total score of FAQLQ-CF administered to a peanut allergic subject at a first time point during the dosing phase of oral immunotherapy. In some embodiments, at a second time point after oral immunotherapy, there is an improvement of at least 0.5 points in the score of the domain of FAQLQ-CF administered to a peanut allergic subject, such as at least 0.5 points in the allergen avoidance and diet restriction domain, at least 0.5 points in the emotional impact domain, and/or at least 0.5 points in the accidental exposure risk domain, as compared to the score in each domain at the first time point prior to oral immunotherapy or during the dosing phase of oral immunotherapy. In some embodiments, the subject is informed that they will be administered a peanut composition prior to oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises a dosing phase. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is FAQLQ-CF. In some embodiments, the total score of FAQLQ-CF administered to a peanut allergic subject at a first time point prior to informing them that they will be or are administering a peanut composition according to an oral immunotherapy plan is 4 or higher. In some embodiments, the score for one or more domains of FAQLQ-CF administered to a peanut allergic subject at a first time point prior to informing the subject that the peanut composition will be or is being administered according to an oral immunotherapy plan is 4 or higher, such as a score in the allergen avoidance and diet restriction domains of 4 or higher, a score in the mood influencing domain of 4 or higher, and/or a score in the accidental exposure risk domain of 4 or higher. In some embodiments, there is at least a 0.5 point improvement, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the overall score of the FAQLQ-CF administered to the peanut allergic subject at a second time point after the time period after they are told to be administered or are being administered a peanut composition according to the oral immunotherapy plan, as compared to the overall score of the FAQLQ-CF administered to the subject prior to the tolling. In some embodiments, at a second time point after advising the subject that the peanut composition will be or is being administered according to the oral immunotherapy plan, there is at least a 0.5 point improvement in the score of the domain of FAQLQ-CF administered to the peanut allergic subject compared to the score in each domain at the time point prior to the advising, such as at least 0.5 point in the allergen avoidance and diet restriction domain, at least 0.5 point in the estrual impact domain, and/or at least 0.5 point in the accidental exposure risk domain. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least one month of treatment. In some embodiments, the time period between the first time point and the second time point comprises a dosing phase of oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is FAQLQ-TF. In some embodiments, the total score of FAQLQ-TF administered to a peanut allergic subject at a first time point prior to or during the dosing phase of oral immunotherapy is 4 or higher. In some embodiments, at a first time point prior to or during the dosing phase of oral immunotherapy, the one or more domains of FAQLQ-TF administered to peanut allergic subjects score 4 or higher, such as score 4 or higher in the allergen avoidance and diet restriction domains, score 4 or higher in the mood affecting domain, and/or score 4 or higher in the accidental exposure risk domain. In some embodiments, there is at least a 0.5 point improvement, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of FAQLQ-TF administered to the subject at a second time point after the period of oral immunotherapy as compared to the total score of FAQLQ-TF administered to a peanut allergic subject at a first time point prior to oral immunotherapy. In some embodiments, there is at least a 0.5 point improvement, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of FAQLQ-TF administered to the subject at a second time point after the period of oral immunotherapy as compared to the total score of FAQLQ-TF administered to peanut allergic subjects at the first time point during the dosing phase of oral immunotherapy. In some embodiments, at a second time point after oral immunotherapy, there is an improvement of at least 0.5 points in the score for the domain of FAQLQ-TF administered to a peanut allergic subject, such as at least 0.5 points in the allergen avoidance and diet restriction domain, at least 0.5 points in the emotional impact domain, and/or at least 0.5 points in the accidental exposure risk domain, as compared to the score in each domain at the first time point prior to oral immunotherapy or during the dosing phase of oral immunotherapy. In some embodiments, the subject is informed that they will be administered a peanut composition prior to oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises a dosing phase. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is FAQLQ-TF. In some embodiments, the total score of FAQLQ-TF administered to a peanut allergic subject at a first time point prior to informing them that they will be or are administering a peanut composition according to an oral immunotherapy plan is 4 or higher. In some embodiments, the score for one or more domains of FAQLQ-TF administered to a peanut allergic subject at a first time point prior to informing the subject that the peanut composition will be or is being administered according to an oral immunotherapy plan is 4 or higher, such as a score in the allergen avoidance and diet restriction domains of 4 or higher, a score in the mood influencing domain of 4 or higher, and/or a score in the accidental exposure risk domain of 4 or higher. In some embodiments, there is at least a 0.5 point improvement, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of the FAQLQ-TF administered to the peanut allergic subject at a second time point after the time period after they are told to be administered or are being administered a peanut composition according to the oral immunotherapy plan, as compared to the total score of the FAQLQ-TF administered to the subject at the first time point prior to the tolling. In some embodiments, at a second time point after advising the subject that the peanut composition will be or is being administered according to the oral immunotherapy plan, there is at least a 0.5 point improvement in the score of the domain of FAQLQ-TF administered to the peanut allergic subject compared to the score in each domain at the first time point prior to the advising, such as at least 0.5 point in the allergen avoidance and diet restriction domain, at least 0.5 point in the emotional impact domain, and/or at least 0.5 point in the accidental exposure risk domain. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least one month of oral immunotherapy. In some embodiments, the time period between the first time point and the second time point comprises a dosing phase of oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is FAQLQ-AF. In some embodiments, the total score of the FAQLQ-AF administered to a peanut allergic subject at a first time point prior to or during the dosing phase of the oral immunotherapy is 4 or higher. In some embodiments, the one or more domains of FAQLQ-AF administered to a peanut allergic subject have a score of 4 or greater at a first time point prior to or during the dosing phase of oral immunotherapy, such as a score of 4 or greater in the allergen avoidance and dietary restriction domains, a score of 4 or greater in the mood affecting domain, a score of 4 or greater in the food allergy-related health domain, and/or a score of 4 or greater in the accidental exposure risk domain. In some embodiments, the overall score of FAQLQ-AF administered to the subject at a second time point after the period of oral immunotherapy is improved by at least 0.5 points, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, compared to the overall score of FAQLQ-AF administered to a peanut allergic subject at a first time point prior to oral immunotherapy. In some embodiments, there is an improvement of at least 0.5 points, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of FAQLQ-AF administered to the subject at a second time point after the period of oral immunotherapy as compared to the total score of FAQLQ-AF administered to a peanut allergic subject at a first time point during the dosing phase of oral immunotherapy. In some embodiments, at a second time point after oral immunotherapy, there is an improvement of at least 0.5 points in the score of the domain of FAQLQ-AF administered to a peanut allergic subject compared to the score in each domain at the first time point prior to oral immunotherapy or during the dosing phase of oral immunotherapy, such as at least 0.5 points in the allergen avoidance and diet restriction domain, at least 0.5 points in the emotional impact domain, at least 0.5 points in the food allergy-related health domain, and/or at least 0.5 points in the accidental exposure risk domain. In some embodiments, the subject is informed that they will be administered a peanut composition prior to oral immunotherapy. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point comprises a dosing phase of oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is FAQLQ-AF. In some embodiments, the total score of FAQLQ-TF administered to a peanut allergic subject at a first time point prior to informing them that they will be or are administering a peanut composition according to an oral immunotherapy plan is 4 or higher. In some embodiments, the one or more domains of FAQLQ-AF administered to a peanut allergic subject at a first time point prior to advising the subject that the subject will or is administering a peanut composition according to an oral immunotherapy plan are scored 4 or higher, such as scored 4 or higher in the allergen avoidance and diet restriction domains, scored 4 or higher in the mood affecting domain, scored 4 or higher in the food allergy-related health domain, and/or scored 4 or higher in the accidental exposure risk domain. In some embodiments, there is at least a 0.5 point improvement, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of FAQLQ-AF administered to the peanut allergic subject at a second time point after the time period after they are told to be administered or are being administered a peanut composition according to the oral immunotherapy plan, as compared to the total score of FAQLQ-AF administered to the subject prior to the tolling. In some embodiments, at a second time point after advising the subject that the peanut composition will be or is being administered according to the oral immunotherapy plan, there is an improvement of at least 0.5 points in the score of the domain of FAQLQ-AF administered to the peanut allergic subject compared to the score in each domain at the first time point prior to the advising, such as at least 0.5 points in the allergen avoidance and diet restriction domain, at least 0.5 points in the mood affecting domain, at least 0.5 points in the food allergy-related health domain, and/or at least 0.5 points in the accidental exposure risk domain. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least one month of treatment. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point comprises a dosing phase of oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is a FAQLQ-PF reported by an agent administered to the caregiver of the subject. In some embodiments, the total score of the FAQLQ-PF administered to the caregiver of the subject at a first time point prior to or during the dosing phase of the oral immunotherapy is 4 or higher. In some embodiments, at a first point in time prior to or during the dosing phase of the oral immunotherapy, the score of one or more domains of FAQLQ-PF administered to the caregiver of the subject is 4 or higher, such as a score of 4 or higher in the mood-affecting domain, a score of 4 or higher in the food-related anxiety domain, and/or a score of 4 or higher in the diet and social restriction domain. In some embodiments, there is at least a 0.5 point improvement, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of the FAQLQ-PF administered to the caregiver of the subject at a second time point after the period of oral immunotherapy compared to the total score of the FAQLQ-PF administered to the caregiver of the subject at the first time point prior to oral immunotherapy. In some embodiments, there is an improvement of at least 0.5 points, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of the FAQLQ-PF administered to the caregiver of the subject at a second time point after the period of oral immunotherapy as compared to the total score of the FAQLQ-PF administered to the caregiver of the subject at the first time point during the medicated phase of oral immunotherapy. In some embodiments, at a second time point after the oral immunotherapy, the domain of FAQLQ-PF administered to the caregiver of the subject has a score that is improved by at least 0.5 points, such as at least 0.5 points in the mood-affecting domain, at least 0.5 points in the food-related anxiety domain, and/or at least 0.5 points in the dietary and social restriction domain, as compared to the score in each domain at the first time point prior to the oral immunotherapy or during the dosing phase of the oral immunotherapy. In some embodiments, the subject is informed that they will be administered a peanut composition prior to oral immunotherapy. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point comprises a dosing phase of oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is a FAQLQ-PF reported by an agent administered to the caregiver of the subject. In some embodiments, the total score of the FAQLQ-PF administered to the caregiver of the subject at the first time point prior to informing the subject that the peanut composition is to be administered or is being administered to them according to the oral immunotherapy plan is 4 or greater. In some embodiments, the score of one or more domains of FAQLQ-PF administered to the caregiver of the subject at a first time point prior to informing the subject that the peanut composition will be or is being administered to them according to an oral immunotherapy plan is 4 or higher, such as a score of 4 or higher in the mood-affecting domain, a score of 4 or higher in the food-related anxiety domain, and/or a score of 4 or higher in the dietary and social restrictions domain. In some embodiments, there is at least a 0.5 point improvement, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of the FAQLQ-PF administered to the caregiver of the subject at a second time point after the time period after the subject is told that the peanut composition will be or is being administered to them according to the oral immunotherapy plan, as compared to the total score of the FAQLQ-PF administered to the caregiver of the subject at the first time point prior to the told of the subject. In some embodiments, at a second time point after the time period after advising the subject that the peanut composition will be or is being administered to them according to the oral immunotherapy plan, there is an improvement of at least 0.5 points in the score for the domain of FAQLQ-PF administered to the caregiver of the subject compared to the score in each domain at the first time point before advising, such as at least 0.5 points in the mood affecting domain, at least 0.5 points in the food-related anxiety domain, and/or at least 0.5 points in the diet and social limitations domain. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least one month of oral immunotherapy. In some embodiments, the time period of oral immunotherapy between the first time point and the second time point comprises a dosing phase of oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is FAIM. In some embodiments, the total score of FAIM administered to a peanut allergic subject at a first time point prior to or during a dosing phase of the oral immunotherapy is 4 or greater. In some embodiments, the total score of FAIM administered to the subject after the second time point after the period of oral immunotherapy is improved by at least 0.5 points, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, compared to the total score of FAIM administered to a peanut allergic subject at the first time point before the oral immunotherapy. In some embodiments, the total score of FAIM administered to the subject at a second time point after the period of oral immunotherapy is improved by at least 0.5 points, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, compared to the total score of FAIM administered to peanut allergic subjects at the first time point during the dosing phase of oral immunotherapy. In some embodiments, the subject is informed that they will be administered a peanut composition prior to oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises a dosing phase. In some embodiments, the period of oral immunotherapy between the first time point and the second time point comprises at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

In some embodiments, the quality of life of a peanut allergic subject is determined by one or more qolqs, wherein at least one QoLQ is FAIM. In some embodiments, the total score of FAIM administered to peanut allergic subjects at a first time point before they are informed that they will be or are being administered a peanut composition according to an oral immunotherapy plan is 4 or greater. In some embodiments, there is at least a 0.5 point improvement, such as at least 1 point, at least 2 points, at least 3 points, or at least 4 points, in the total score of FAIM administered to the peanut allergic subject at a second time point after the time period after they are told to be administered or are being administered a peanut composition according to the oral immunotherapy plan, as compared to the total score of FAIM administered to the subject at the first time point prior to the tolling. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least one month of treatment. In some embodiments, the time period between the first time point and the second time point comprises a dosing phase of oral immunotherapy. In some embodiments, the period of oral immunotherapy between the first time point and the second time point is at least 1 month of maintenance therapy, such as at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 12 months of maintenance therapy.

Peanut oral immunotherapy

In some embodiments, during the course of oral immunotherapy, the quality of life of a subject may be improved by administering a range of doses of a peanut protein composition to a peanut allergic subject according to a dosing schedule. In some embodiments, during the course of oral immunotherapy, the quality of life of a subject may be improved by informing a peanut allergic subject that a range of doses of a peanut protein composition is to be administered or is being administered to the subject according to a dosing schedule. In some embodiments, during the course of oral immunotherapy, the quality of life of a subject may be improved by instructing the caregiver of the subject to inform the peanut allergic subject that a range of doses of the peanut protein composition are to be or are being administered to the subject according to a dosing schedule.

The overall length of the oral immunotherapy (e.g., the duration of the medicated phase) may vary depending on age, health condition, nature and type of peanut allergy, concurrent interventions, and/or complex indications, among others. The therapy is typically multi-staged and includes at least a dosing phase and a maintenance phase. In some embodiments, oral immunotherapy may also include an initial escalation phase prior to the dosing phase. The dose of peanut protein composition administered during the dosing and maintenance phases can be periodically adjusted or scheduled to increase, decrease, or remain the same. The dose size of the peanut protein composition administered during the dosing and maintenance phases can be adjusted as needed based on the judgment of the medical caregiver of the subject and/or the needs of the subject.

Methods of diagnosing peanut allergy are known in the art and include immunoassays (such as peanut-specific IgE), skin prick tests, food challenge and experimental exclusion diets. To diagnose peanut allergy by food challenge, subjects received increasing doses of peanut protein. The allergic reaction to peanut proteins observed during food challenge indicates that the subject has peanut allergy and is a candidate for peanut oral immunotherapy. The decision whether a subject will respond to a particular dose during a food challenge depends on the test criteria, which may vary. The response in a food challenge may be judged by the severity of the symptoms (e.g., mild, moderate, or severe) and/or the observability of the symptoms (e.g., whether the symptoms are subjectively reported by the patient or objectively observed by a healthcare worker).

A subject that is treated with peanut OIT as described herein to improve the quality of life of the subject is known or suspected to be allergic to peanut. In some embodiments, the subject has previously attempted or completed peanut protein OIT. In some embodiments, the prior peanut protein OIT is ineffective (e.g., due to failure to induce acceptable desensitization, produce unacceptable allergic adverse reactions, fail to confer sufficient protection to prevent accidental exposure to peanut protein, or fail to improve the quality of life of the subject), is terminated by the patient due to discomfort, inconvenience (e.g., due to daily dosing or frequent clinical visits), or necessity (e.g., due to reaction to peanut protein doses and/or due to allergic adverse events during OIT), or is terminated by the healthcare provider who terminated the patient (e.g., due to allergic adverse reactions to peanut protein doses and/or due to allergic adverse events during OIT).

As described herein, a subject receiving peanut OIT treatment to improve the quality of life of the subject may be untreated, never receiving peanut OIT treatment to improve their quality of life. Subjects diagnosed with peanut allergy by diagnostic exposure to peanut protein (such as in a food challenge, but without a history of other clinical exposure to peanut protein) are still considered untreated after diagnostic exposure for the purposes of this application.

Subjects receiving oral immunotherapy treatment to improve their quality of life are human subjects. In some embodiments, the subject is more than about 12 months, such as from about 12 months to about 48 months (e.g., from about 12 months to about 24 months, from about 24 months to about 36 months, or from about 36 months to about 48 months). In some embodiments, the subject is about 4 years old or older. In some embodiments, the subject is between 4 and less than 18 years of age. In some embodiments, the subject is over 18 years of age.

The dosing phase precedes the maintenance phase and comprises administering a series of incremental doses to achieve a maximum dose administered to the subject during oral immunotherapy. The length of the medicated phase can be adjusted according to the needs of the individual patient, but is typically completed in about 22 to about 40 weeks. For some patients, the medicated phase may last up to 2 years or more. For example, if a patient experiences an allergic adverse event after starting a higher dose in the dose series, the dosing phase may be extended.

The dosing phase of peanut OIT generally involves incrementally increasing the dose of peanut protein administered over a period of time (e.g., approximately every 1 to 4 weeks). A particular dose in a series is repeatedly (e.g., daily) administered to a patient until proceeding to the next dose in the series. In some cases, such as when a subject is intolerant to a particular dose in a series or the subject experiences one or more allergic adverse events, the dose is reduced or repeated for a period of time in the series before advancing to the next dose in the series. The rate of dosing (e.g., the length of time that individual doses in a series are administered or the size of dose increments between doses in a series) can be adjusted based on one or more observed allergic adverse events.

Optionally, the oral immunotherapy comprises an initial escalation phase prior to the dosing phase, wherein a series of escalated doses are administered to the subject over the course of one or two days. The initial escalation phase differs from the dosing phase in that it has a lower dose range, shorter dose escalation intervals, and is generally more closely monitored by the medical caregiver of the subject. For example, an initial increment of two days may include a series of doses of about 0.5mg to about 6mg peanut protein, such as a single dose of about 0.5mg, about 1mg, about 1.5mg, about 3mg, and about 6mg peanut protein. The highest tolerated dose in the initial escalation phase or a dose lower than the highest tolerated dose in the initial escalation phase may be the first dose of the dosing phase. A subject may be excluded from oral immunotherapy if the subject does not tolerate at least a certain dose during the initial escalation phase. For example, if a subject experiences a severe allergic adverse event after administration of a 0.5mg, 1mg, or 1.5mg peanut protein dose, the subject may not be allowed to proceed to the dosing phase. The purpose of the initial escalation phase includes calibrating the dose of the dosing phase (e.g., the initial dose of the dosing phase), and ensuring that the subject is eligible to safely follow the dosing phase.

Prior to, during, or after oral immunotherapy (such as prior to, during, or after a dosing phase, or prior to, during, or after a maintenance phase), peanut allergic subjects and/or caregivers of the subjects may receive a quality of life assessment.

Maintenance phase dosing schedule

The maintenance phase of peanut oral immunotherapy begins after the highest dose of the dosing phase is reached. The maintenance phase is longer than about 24 weeks or more and may last for the entire life of the patient. For example, the length of the maintenance phase may be more than about 28 weeks, more than about 32 weeks, more than about 36 weeks, more than about 40 weeks, more than about 44 weeks, or more than about 48 weeks. In some embodiments, the maintenance phase is about 24 weeks to about 28 weeks, about 28 weeks to about 32 weeks, about 32 weeks to about 36 weeks, about 36 weeks to about 40 weeks, about 40 weeks to about 44 weeks, about 44 weeks to about 48 weeks, about 48 weeks to about 52 weeks, about 52 weeks to about 60 weeks, about 60 weeks to about 72 weeks, about 72 weeks to about 80 weeks, or more than about 80 weeks, such as the lifetime of the subject. In some embodiments, the maintenance phase is up to about 108 weeks.

In some embodiments, the maintenance phase dose is administered to the subject daily during at least a portion of the maintenance phase. In some embodiments, the maintenance phase dose is administered to the subject daily for about 6 months to about 2 years, such as about 6 months, about 6 months to about 12 months, about 12 months to about 18 months, or about 18 months to about 2 years, during the maintenance phase.

The dose of peanut protein administered to the subject during the maintenance phase is between about 200mg and about 1,000mg of peanut protein. For example, in some embodiments, the dose during the maintenance phase is between or is a value and range between about 200mg and about 300mg peanut protein, about 300mg and about 500mg peanut protein, about 500mg and about 1,000mg peanut protein. In an exemplary embodiment, the maintenance phase dose administered to the subject during the maintenance phase is about 300mg peanut protein.

Dosing stage

The medicated phase of oral immunotherapy involves administering a series of escalating doses to the patient, starting at a lower dose than the highest dose of oral immunotherapy and ending at the highest dose of oral immunotherapy. Each dose in the series of doses is administered periodically, such as daily. Each dose in the series may comprise administering the peanut protein composition daily for a period of time, such as from about 1 week to about 4 weeks, such as about 2 weeks. After a certain dose in the series is completed for a period of time, the treatment may be advanced to a higher dose in the series. In some embodiments, the dosing phase of treatment comprises a series of between 2 and 10 different dose levels. If the subject tolerates a particular dose level for a period of time during the dosing phase, the subject can proceed to the next dose level in the series of dosing phases. If the subject is unable to tolerate a particular dose level for a period of time during the dosing phase, the subject may repeat the current dose level in the series. Alternatively, if the subject is unable to tolerate a particular dose level for a period of time during the dosing phase, the subject may return to an earlier dose level in the series. Thus, the duration of the dosing phase depends on the specific response of the subject. The subject may repeat the doses in the series as many times as necessary to achieve the highest dose in the series. The dosing phase was ended when the highest dose was tolerated for two weeks.

The pharmaceutical composition of the dose of peanut protein administered during the dosing phase comprises between about 0.5mg and about 5,000mg of peanut protein, such as about 0.5mg to about 10mg of peanut protein, about 10mg to about 100mg of peanut protein, about 100mg to about 300mg of peanut protein, about 300mg to about 500mg of peanut protein, about 500mg to about 1,000mg of peanut protein, about 1,000mg to about 2,000mg of peanut protein, or about 2,000mg to about 5,000mg of peanut protein, and values and ranges therebetween. In a non-limiting exemplary embodiment, the dose of the dosing phase is a maximum tolerated dose (such as 3mg or 6mg peanut protein) administered daily for an initial escalation phase, followed by a series of doses of about 12mg peanut protein, about 20mg peanut protein, about 40mg peanut protein, about 80mg peanut protein, about 120mg peanut protein, about 160mg peanut protein, about 200mg peanut protein, about 240mg peanut protein, and about 300mg peanut protein administered daily, wherein each dose level is administered for about 1 week to about 4 weeks (such as about 2 weeks) before advancing to the next dose in the series. In another exemplary embodiment, the dose of the dosing phase is the maximum tolerated dose (such as 3mg or 6mg peanut protein) administered daily for an initial escalation phase, followed by a series of escalating daily doses prescribed by the healthcare professional administering the subject daily, wherein each daily dose comprises one or more capsules or sachets selected from the group consisting of: 0.5mg peanut protein capsule, 1mg peanut protein capsule, 10mg peanut protein capsule, 20mg peanut protein capsule, 100mg peanut protein capsule, or 300mg peanut protein sachet, wherein each dose level is administered for about 1 week to about 4 weeks (such as about 2 weeks) before advancing to the next dose in the series.

The series of doses of the dosing phase is distinguished by adjusting the dose administered. The dose size in the series of doses of the dosing phase is adjusted periodically, such as once every week to once every six weeks. In some embodiments, the dosing phase comprises weekly dose adjustments, biweekly dose adjustments, every three weeks dose adjustments, every four weeks dose adjustments, every five weeks dose adjustments, every six weeks dose adjustments, or adjustments as needed based on the judgment of the medical caregiver of the subject. The dose may be increased to the next planned dose in the series, decreased to the previous dose in the series in response to an allergic adverse event, maintained at the current dose in the series for an additional time interval, increased to a higher dose in the series based on the judgment of the medical caregiver of the subject, or decreased to a lower dose in the series based on the judgment of the medical caregiver of the subject. In some embodiments, the dosing phase is adjusted at any time based on the judgment of the subject's medical caregiver that the subject is intolerant to the current dose in the series.

The dosing phase was carried out until the subject reached the final dose in the dosing series. In some embodiments, the dosing phase is from about 1 month to about 6 months, such as from about 1 month to about 3 months or from about 3 months to about 6 months. In some embodiments, the dosing period is from about 6 months to about 2 years, such as from about 6 months to about 1 year, from about 1 year to about 18 months, or from about 18 months to about 2 years. In a non-limiting exemplary embodiment, the dosing phase lasts 22 weeks to 2 years and terminates with 300mg peanut protein by a dose of 12mg peanut protein, 20mg peanut protein, 40mg peanut protein, 80mg peanut protein, 120mg peanut protein, 160mg peanut protein, 200mg peanut protein, 240mg peanut protein, according to the number of dose reductions and re-increments and dose level repeats. In any of the embodiments described, the dosing phase is terminated when the subject tolerates the planned dose for the final dose in the series of dosing phases for 2 weeks, thereby initiating the maintenance phase.

Each dose in the series of dosing phases can be planned for about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, or values and ranges therebetween. Based on the observation of allergic adverse events, the caregiver of the subject can repeat the current dose for the subject in the dosing series. A particular fraction having a particular dose can be repeated as many times as necessary (such as one, two, three, four or more times) to sufficiently desensitize the subject to the dose, such as when the subject is no longer experiencing moderate or severe adverse allergic events upon accidental (or intentional) exposure to a food allergen.

Initial incremental phase

Optionally, the oral immunotherapy comprises an initial escalation phase prior to the dosing phase. The initial escalation phase may ensure the safety and applicability of oral immunotherapy to a particular subject. The initial incremental phase is administered within a short time (such as one or two days) at an appropriate medical facility (such as a physician's office or an allergy clinic). The subject is typically closely monitored by medical care personnel who can provide intervention in the event of an allergic adverse reaction requiring intervention, such as epinephrine, albuterol, and diphenhydramine. The initial escalation phase of oral immunotherapy, if present, comprises administering multiple small doses of a peanut protein composition to a subject. The small doses may be separated by a period of time, such as about 10 minutes to about 60 minutes, and may include 1, 2, 3, 4, or 5 or more doses.

The initial up-phase may include a dose of between about 0.5mg and about 6mg peanut protein (such as about 0.5mg to about 1.5mg peanut protein, about 1.5mg to about 3mg peanut protein, or about 3mg to about 6mg peanut protein). In a non-limiting example, the initial escalation phase comprises an increment from about 0.5mg peanut protein up to a maximum of about 6mg peanut protein over a day, wherein a single dose is about 0.5mg, about 1mg, about 1.5mg, about 3mg and about 6mg peanut protein, wherein tolerance of a 3mg or 6mg peanut protein dose indicates that the subject can safely proceed to the dosing phase of oral immunotherapy.

Composition for oral immunotherapy

Exemplary compositions for treating peanut allergy are described in detail in U.S. publication 2014/0271721, the contents of which are incorporated herein by reference in their entirety. Exemplary methods for preparing peanut protein formulations are described in detail in U.S. publication 2014/0271836, the contents of which are incorporated herein by reference in their entirety.

By administering a range of doses of a peanut protein composition to a subject during the course of an oral immunotherapy with peanut protein, the quality of life of a peanut allergic subject can be improved. The peanut protein composition is preferably a pharmaceutical composition comprising one or more peanut allergen proteins for use in the treatment of peanut allergy. In some embodiments, peanut proteins can be isolated from peanut flour and optionally further comprise one or more diluents, one or more glidants, and/or one or more lubricants. In some embodiments, the pharmaceutical composition of peanut proteins comprises from about 0.05% to about 100% w/w peanut proteins.

In some embodiments, the pharmaceutical composition of peanut proteins comprises a peanut protein as characterized. In some embodiments, the characterized peanut protein comprises the characterized peanut allergen proteins Ara h1, Ara h2, and/or Ara h 6. In one embodiment, the final formulation for treating peanut allergy comprises peanut flour comprising the characterized peanut allergen proteins Ara h1, Ara h2, and/or Ara h6 formulated with diluents, glidants, and lubricants in graded doses comprising capsules containing between about 0.5mg and about 5,000mg of peanut protein for administration during the dosing, maintenance, and/or initial up-dosing phase of oral immunotherapy.

In any of the methods described herein, the pharmaceutical composition for peanut protein administered in the maintenance phase of oral immunotherapy may comprise a dose of between about 200mg and about 1,000mg of peanut protein (such as between about 200mg and about 250mg peanut protein, between about 250mg and about 300mg peanut protein, between about 300mg and about 500mg peanut protein, and between about 500mg and about 1,000mg peanut protein). In a non-limiting preferred embodiment, the dose of peanut protein for administration during the maintenance phase of oral immunotherapy is about 300mg peanut protein.

In some embodiments, the pharmaceutical composition of peanut protein for administration during the dosing phase of oral immunotherapy comprises between about 0.5mg and about 5,000mg of peanut protein, such as a single dose in a series of about 3mg, about 6mg, about 10mg, about 12mg, about 20mg, about 40mg, about 80mg, about 100mg, about 120mg, about 160mg, about 200mg, about 240mg, and about 300mg of peanut protein. In non-limiting exemplary embodiments, the dose of peanut protein for administration in the dosing phase of oral immunotherapy is the maximum tolerated dose for the initial escalation phase of daily administration (such as about 3mg peanut protein or about 6mg peanut protein) followed by daily administration of a series of escalating daily doses prescribed by the healthcare professional of the subject, wherein each daily dose comprises one or more capsules or sachets selected from the group consisting of: about 0.5mg peanut protein capsule, about 1mg peanut protein capsule, about 10mg peanut protein capsule, about 20mg peanut protein capsule, about 100mg peanut protein capsule, or about 300mg peanut protein sachet, wherein each dose level is administered for about 1 week to about 4 weeks (such as about 2 weeks) before advancing to the next dose.

In the methods described herein, oral immunotherapy may optionally include an initial escalation phase. In some embodiments, the pharmaceutical composition for peanut protein administered during the initial escalation phase of oral immunotherapy comprises between about 0.5mg and about 6mg peanut protein, such as a single dose of about 0.5mg, about 1mg, about 1.5mg, about 3mg, and about 6mg peanut protein. In some embodiments, the pharmaceutical composition of peanut protein for administration during the initial escalation phase of oral immunotherapy comprises between about 0.5mg and about 6mg of peanut protein, such as a single dose of about 0.5mg, about 1mg, about 1.5mg, about 3mg, about 6mg, and about 12mg of peanut protein.

Exemplary embodiments

The invention may be better understood by reference to the following exemplary embodiments. However, these exemplary embodiments are not intended to limit the scope of the invention described herein.

Embodiment 1. a method of improving the quality of life of a peanut allergic patient comprises: administering a peanut composition to the patient according to an oral immunotherapy plan.

Embodiment 2. the method of embodiment 1, wherein the patient is informed that the peanut composition is being administered.

Embodiment 3. the method of embodiment 2, wherein the patient is informed that the peanut composition is being administered to the patient at the beginning of the oral immunotherapy plan.

Embodiment 4. the method of embodiment 2, wherein the patient is informed that the peanut composition is being administered to the patient during a dosing phase of the oral immunotherapy plan.

Embodiment 5. the method of embodiment 2, wherein the patient is informed that the peanut composition is being administered to the patient during a maintenance phase of the oral immunotherapy plan.

Embodiment 6. the method of embodiment 1, further comprising informing the patient that the peanut composition is being administered to the patient.

Embodiment 7. the method of embodiment 6, wherein the patient is informed that the peanut composition is being administered to the patient prior to the start of the oral immunotherapy plan.

Embodiment 8 the method of embodiment 6, wherein the patient is informed that the peanut composition is being administered to the patient during a dosing phase of an oral immunotherapy plan.

Embodiment 9 the method of embodiment 6, wherein the patient is informed that the peanut composition is being administered to the patient during a maintenance phase of the oral immunotherapy plan.

Embodiment 10. the method of any one of embodiments 1 to 9, wherein the improvement in quality of life is measured using a quality of life questionnaire (QoLQ).

Embodiment 11 the method of embodiment 10, wherein the QoLQ comprises one or more scored measurement domains.

Embodiment 12. the method of embodiment 11, wherein the QoLQ is a Food Allergy Quality of Life Questionnaire (FAQLQ).

Embodiment 13 the method of embodiment 12, wherein the FAQLQ is FAQLQ-childhood table (FAQLQ-CF), FAQLQ-minor-year table (FAQLQ-TF), FAQLQ-adult table (FAQLQ-AF), or FAQLQ-father-mother table (FAQLQ-PF).

Embodiment 14. the method of embodiment 10, wherein the QoLQ is a Food Allergy Independent Measure (FAIM).

Embodiment 15 the method of embodiment 14, wherein the FAIM is FAIM-childhood table (FAIM-CF), FAIM-minor-year table (FAIM-TF), FAIM-adult table (FAIM-AF), or FAIM-father-mother table (FAIM-PF).

Embodiment 16. a method of improving the quality of life of a peanut allergic patient, as assessed by the quality of life questionnaire (QoLQ), comprising administering a peanut composition to the patient according to an oral immunotherapy plan.

Embodiment 17 the method of embodiment 16, wherein the patient is informed that the peanut composition is being administered.

Embodiment 18 the method of embodiment 17, wherein the patient is informed that the peanut composition is being administered to the patient at the beginning of the oral immunotherapy plan.

Embodiment 19 the method of embodiment 17, wherein the patient is informed that the peanut composition is being administered to the patient during a dosing phase of the oral immunotherapy plan.

Embodiment 20 the method of embodiment 17, wherein the patient is informed that the peanut composition is being administered to the patient during a maintenance phase of the oral immunotherapy plan.

Embodiment 21. the method of embodiment 16, further comprising informing the patient that the peanut composition is being administered to the patient.

Embodiment 22 the method of embodiment 21, wherein the patient is informed that the peanut composition is being administered to the patient prior to the start of the oral immunotherapy plan.

Embodiment 23 the method of embodiment 21, wherein the patient is informed that the peanut composition is being administered to the patient during a dosing phase of an oral immunotherapy plan.

Embodiment 24 the method of embodiment 21, wherein the patient is informed that the peanut composition is being administered to the patient during a maintenance phase of the oral immunotherapy plan.

Embodiment 25 the method of any one of embodiments 16 to 24, wherein the QoLQ comprises one or more scored measurement fields.

Embodiment 26. the method of embodiment 25, wherein the QoLQ is a Food Allergy Quality of Life Questionnaire (FAQLQ).

Embodiment 27. the method of embodiment 26, wherein the FAQLQ is FAQLQ-childhood table (FAQLQ-CF), FAQLQ-minor-year table (FAQLQ-TF), FAQLQ-adult table (FAQLQ-AF), or FAQLQ-father-mother table (FAQLQ-PF).

Embodiment 28. the method of embodiment 25, wherein the QoLQ is a Food Allergy Independent Measure (FAIM).

Embodiment 29 the method of embodiment 28, wherein the FAIM is FAIM-childhood table (FAIM-CF), FAIM-minor-year table (FAIM-TF), FAIM-adult table (FAIM-AF), or FAIM-father-mother table (FAIM-PF).

Embodiment 30. the method of embodiment 25, wherein said QoLQ is a pediatric quality of life manifest (PedsQL).

Embodiment 31 the method of any one of embodiments 1 to 30, wherein the quality of life is improved for at least 6 months.

Embodiment 32 the method of any one of embodiments 1 to 31, wherein the quality of life is improved for at least 12 months.

Embodiment 33 the method of any one of embodiments 11 to 13 or 25 to 27, wherein the one or more score domains of the QoLQ each score on a scale between 1 and 7, or each convert to a score between a first score and a second score, wherein the second score indicates poor quality of life.

Embodiment 34 the method of any one of embodiments 11 to 13 or 25 to 27, wherein the patient's quality of life is at least a 0.5 point improvement in one or more domains of the QoLQ at a second time point after the period of oral immunotherapy compared to the assessment at the first time point before the period of oral immunotherapy.

Embodiment 35 the method of any one of embodiments 11 to 17 or 25 to 34, wherein the patient's quality of life is at least a 0.5 point improvement in the total score of QoLQ at a second time point after the period of oral immunotherapy compared to the assessment at the first time point prior to the period of oral immunotherapy; wherein the total score is an average of the scores of each domain.

Embodiment 36 the method of embodiment 34 or embodiment 35, wherein the period of oral immunotherapy between the first time point and the second time point is the medicated phase of the oral immunotherapy plan.

Embodiment 37 the method of embodiment 34 or embodiment 35, wherein the period of oral immunotherapy between the first time point and the second time point is at least 1 month of maintenance therapy for which the oral immunotherapy is planned.

Embodiment 38 the method of any one of embodiments 1 to 37, wherein the quality of life improves after 6 months of the oral immunotherapy plan.

Embodiment 39 the method of any one of embodiments 1 to 38, wherein the oral immunotherapy plan comprises a dosing phase and a maintenance phase.

Embodiment 40. the method of embodiment 39, wherein the peanut composition is administered to the patient daily during the maintenance phase.

Embodiment 41 the method of embodiment 39 or embodiment 40, wherein the maintenance phase is at least 3 months.

Embodiment 42 the method of any one of embodiments 39 to 41, wherein the peanut composition is administered to the patient at a dose of about 300mg peanut protein or more during a maintenance phase of the oral immunotherapy plan.

Embodiment 43 the method of any one of embodiments 39 to 42, wherein the medicated phase comprises administering to the patient two or more different doses between about 3mg and the dose of about the initial maintenance phase dose.

Embodiment 44 the method according to any one of embodiments 1 to 43, wherein the oral immunotherapy plan comprises a dosing phase of between about 3 months and about 2 years in length.

Embodiment 45 the method of any one of embodiments 1 to 44, wherein the oral immunotherapy plan further comprises an initial escalation phase.

Embodiment 46. the method of any one of embodiments 1 to 45, wherein the patient is about 4 years old or older.

Embodiment 47 the method of any one of embodiments 1 to 46, wherein the patient is between about 4 and about 17 years of age.

Embodiment 48 the method of any one of embodiments 1 to 47, wherein the patient is between about 8 and about 17 years of age.

Embodiment 49 the method of any one of embodiments 1 to 48, wherein the method comprises measuring the quality of life prior to administering a peanut composition to the patient according to an oral immunotherapy plan.

Embodiment 50 the method of any one of embodiments 1 to 49, wherein the method comprises measuring the quality of life after administering a peanut composition to the patient according to an oral immunotherapy plan.

Embodiment 51. the method of any one of embodiments 2 to 15 or 17 to 50, wherein the method comprises measuring the quality of life after informing the patient that the peanut composition is being administered.

Embodiment 52. the method of any one of embodiments 1 to 51, wherein the quality of life of the patient is improved as determined by a quality of life questionnaire (QoLQ).

Examples

The present application may be better understood by reference to the following non-limiting examples provided as exemplary embodiments of the present application. The following examples are given to more fully illustrate the embodiments, however, should in no way be construed as limiting the broad scope of the application. While certain embodiments of the present application have been shown and described herein, it will be obvious that such embodiments are provided by way of example only. Numerous modifications, changes, and substitutions will occur to those skilled in the art without departing from the spirit and scope of the present invention. It should be understood that various alternatives to the embodiments described herein may be employed in practicing the methods described herein.

Example 1 Effect of peanut allergy on quality of Life

A study was conducted to assess the actual burden of peanut allergy on american patients and caregivers.

In part of the study, self-reported, providers diagnosed peanut allergic 13-17 year old adolescents and caregivers of 13-17 year old adolescents completed a validated, age-appropriate food allergy quality of life questionnaire (either FAQLQ-TF for self-reporting or FAQLQ-PF for agent reporting; where 1 is no question and 7 is an extreme question for each answer). Inter-group analysis (chi-square; t-test) was performed. Teenagers (n ═ 102) and teenagers' caregivers (n ═ 94) completed the survey. Key demographic variables and disease history variables (self-reported versus agent-reported) in adolescents are similar. With respect to caregivers, teenagers report that peanut allergy imposes greater burden on their daily lives and fear of reactions affecting emotional well-being, and are more careful in avoiding direct contact with peanuts. Teenagers have a higher score (i.e., poorer quality of life) on the FAQLQ mood scale compared to caregiver assessments (mean 5.07 vs. 4.21, p < 0.001). Teenagers, which express more attention on physical symptoms during the reaction and the impact of peanut allergy on family than the caregivers of teenagers, also differ significantly in the most relevant aspects of PA. In summary, teenagers report poorer quality of life (impact on daily life, emotional well-being and FAQLQ emotional scale), greater concern for the physical symptoms of the response and impact on the family, and more careful avoidance of peanut exposure than caregivers.

In the young years of completing self-reporting of FAQLQ-TF, many variables were statistically significantly correlated with the FAQLQ-TF total score: psychosocial variables, including the impact of fear responses on emotional health (p <0.001), daily life restrictions (p <0.001), concerns about entry of adrenergic autoinjectors (p <0.001), confidence in response (p 0.025), total number of advanced interventions used throughout life (ER, hospital, IV epinephrine, or cannula) (p 0.003), and the severity of their most severe response (p 0.006). There was no statistically significant correlation with age, gender, number of other food allergies and other health conditions, time since last response and since last severe response, number of moderate/severe reactions in a lifetime and number of reactions in the last year. These data indicate that psychosocial variables and the need to modify daily activities to practice avoidance, as well as the medical history of the need to seek advanced treatment due to exposure, are associated with reduced disease-specific quality of life.

In another part of the study, self-reported, provider diagnosed peanut allergy teenagers 13 to 17 years of age completed the pediatric quality of life list (PedsQL; score 0 to 100, with higher scores being better quality of life). Inter-group analysis (chi-square; t-test) was performed. The average PedsQL total score for peanut allergic teenagers (n 102) was 48.8. The average sub-scale score was: physical (53.6), emotional (43.0), social (48.2), school (46.0), and psychosocial (44.5). These scores were significantly below the scale scores of the general population aged 8 to 16 years (n > 5900; range 78.2-87.0) and exceeded the minimum clinically significant difference (4.36 to 9.12 points). Teenagers who experience more than 1 peanut allergy-related reaction in the past year have significantly lower total PedsQL scores (p 0.008), as have teenagers who have received clinician intervention of more than 1 peanut allergy in the past year (p 0.001, those who are "completely dissatisfied" to "somewhat satisfied" with current methods of prevention of peanut allergy (p 0.012), those who say that peanut allergy is "somewhat" to "completely" limiting their daily lives (p 0.013), or those who report "great" to "100% chance" of not being able to effectively treat the reaction). Thus, peanut allergic teenagers have significantly lower PedsQL scores than the general population of individuals of similar age. The total petsql score varies significantly between subgroups defined by recent allergic reactions/need for clinician intervention, satisfaction with reaction prevention, perceptual limitations on daily living, and concerns about their ability to handle reactions.

Example 2 peanut oral immunotherapy clinical trial

A) Double blind clinical trials. Randomized, double-blind, placebo-controlled phase 3 clinical trials (PALISADE) were conducted with peanut allergic subjects aged 4 to 49 years. The subject underwent an initial increment, then underwent a dosing phase to reach a target dose of 300mg of peanut protein per day, followed by a maintenance phase of approximately six months, including administration of 300mg of peanut protein per day. See Jones et al, efficiency and Safety of AR101 in Peanout Allergy, Results from a Phase 3, randomised, Double-bind, Placebo-Controlled Trial (PALISADE), J.Allergy Clin.Immunol., Vol.141, No. 2, supplement AB400, 2018; and Vickery et al, AR101 Oral immunology for peanout Allergy, n.engl.j.med., volume 379, p 21, 1991-.

At baseline screening and withdrawal from PALISADE, subjects (self-report) and their parents or guardians/caregivers (attorney reports) completed an age-appropriate food allergy quality of life questionnaire (FAQLQ; e.g., FAQLQ-CF, FAQLQ-TF, or FAQLQ-PF). The parent/caregiver domain and total score were calculated for subjects aged 8 years and 4 to 17 years. To report results throughout the clinical trial, self-reported FAQLQ scores were combined into a single child, juvenile, and adult table (called FAQLQ-CTAF) using common projects (i.e., questions). The scale ranges from 1 to 6 or 1 to 7, with higher scores indicating poorer QoL. Relationships to demographic variables and disease history variables were also evaluated. 367 peanut allergic subjects and 442 parents/caregivers completed the baseline assessment. The results indicate that peanut allergy has a significant impact on the quality of life of the subject. For self-reporting, emotional impact had the highest score (4.80), followed by allergen avoidance and dietary restriction (4.40), and risk of accidental exposure (4.20). For the parent/caregiver, food anxiety had the highest score (4.23), followed by social and dietary restrictions (4.17) and emotional impact (3.82). See Wang et al, Impact of Peanic Allergy on Quality of Life, base Results from PALISADE, a Phase 3, Double-blade, Placebo-Controlled Trial for AR101 Oral Immunotherapy, J.Immunol. 143 Vol.2, 2019.

Subjects (self-report) and their parents or guardians (attorney reports) also completed an age-appropriate food allergy independent measure (FAIM; e.g., FAIM-CF or FAIM-PF) at baseline screening and withdrawal from PALISADE. The FAIM questionnaire consists of expected outcomes and disease severity issues. Each FAIM problem is scored from 1 to 7, with higher scores indicating poor QoL (e.g., perception of maximum severity or poor expectation of outcome).

B) And (4) expanding an open label. Some PALISADE completer treated with active agent (i.e., non-placebo) chose to participate in an Open Label Extension (OLE) follow-up clinical trial in which subjects were informed that they will continue to receive active treatment. Prior to initiating OLE (at PALISADE withdrawal), the subject (self-report) and/or their parent or caregiver/guardian (attorney report) completed the age-appropriate FAQLQ (e.g., FAQLQ-CF, FAQLQ-TF or FAQLQ-PF) or FAIM (e.g., FAIM-CF or FAIM-PF). As described above, to report results throughout the experiment, the FAQLQ scores reported by themselves were combined using a common term. Subjects involved in OLE received an additional maintenance therapy for about 6 months (i.e., about 28 weeks) that included administration of 300mg peanut protein per day. At the end of about another 6 months of OLE maintenance therapy (i.e., after about 52 weeks total daily 300mg peanut protein maintenance therapy), subjects received a withdrawal double-blind placebo-controlled food challenge (DBPCFC). The subject and/or their parents/caregivers complete the withdrawal from the appropriate age of FAQLQ (e.g., FAQLQ-CF, FAQLQ-TF, or FAQLQ-PF) and FAIM (e.g., FAIM-CF or FAIM-PF).

C) And (6) obtaining the result. 110 peanut allergic subjects entered OLE and 103 completed daily maintenance therapy for another 6 months. Of those participating in the OLE trial, 62.7% were between 4 and 11 years of age, and the remaining 37.2% were between 12 and 17 years of age.

In 68 patients between age 8 and 17 who completed the FAQLQ self-assessment at the end of OLE, statistically significant improvements over the minimum clinically significant difference (MCID) reported by the developer were observed in all individual scales (allergy avoidance and dietary restrictions, accidental exposure risks and emotional effects) and total scores (all p <0.01) compared to the FAQLQ PALISADE baseline assessment, as reported in fig. 1. Statistically significant improvement over developer reported MCID was observed in the expected questions and overall scores for the results in 72 patients between 8 and 17 years of age who completed FAIM self-assessment at the end of OLE. For the issues of product avoidance and social impact, a reduction below MCID was observed. Subjects reported improvement in QoL from PALISADE screening to PALISADE withdrawal (blind time period) and PALISADE withdrawal to OLE withdrawal (open label time period). For FAQLQ self-reporting, these changes have similar magnitudes.

As reported in fig. 2, two of the three domains of FAQLQ-PF completed by the parents/guardians also observed statistically significant improvement for 93 peanut allergic subjects participating in OLE (social and dietary restrictions: p < 0.01; food anxiety: p < 0.05; emotional impact: p ═ 0.07) and the overall score was also significant compared to the baseline FAQLQ-PF assessment (p < 0.01). However, none of the agent reported FAQLQ scores exceeded the threshold indicating an MID as reported by the developer. For the FAIM questionnaire, the expected values for the results (by the agent) for the child were collected only from parents/caregivers of children under 13 years of age. Of these 62 parents/caregivers of peanut allergic children who completed OLE, a statistically significant reduction in the expected (by the agent) domain of results was observed for children, although the reduction did not exceed the developer reported MCID. Of the 91 parents/caregivers of peanut allergic children who completed OLE, the expected field of results by the parents/caregivers indicated a statistically significant decrease in the score at the end of OLE time domain. This reduction exceeds the MID reported by developers. The majority of the improvement in QoL reported by the agent compared to self-reported QoL measurements is after informing peanut allergic subjects that they are receiving a peanut protein composition, i.e., after an open label period.

These FAQLQ and FAIM data were also analyzed by variables of food challenge results, adverse events and epinephrine usage. As shown in figure 3, subjects who completed OLE were divided based on tolerance of a 600mg peanut protein dose in OLE withdrawal from the double-blind placebo-controlled food challenge, the occurrence of systemic anaphylaxis during the PALISADE or OLE clinical trial, and the use of epinephrine during the PALISADE or OLE clinical trial. In fig. 3, the surrogate report for FAIM limits the expectation of a result score in children with subjects aged 4 to 12 years. Peanut protein OIT is consistently associated with improvement in self-assessed QoL. The efficacy of OIT (as measured by oral food challenge, presence of systemic anaphylaxis, and use of epinephrine) is associated with a reduction in improvement, but still an improvement compared to baseline. Surprisingly, the improvement in QoL reported by the agent was consistently less significant than the self-assessment, indicating that the parents/caregivers underestimated the improvement in QoL of their children. The difference in QoL reported by the parent/caregiver representative was also more significant than self-assessment in children who did not tolerate a 600mg peanut protein dose in the oral food challenge compared to children who tolerated a 600mg peanut protein dose.

D) Additional processing queues. In addition to the patient cohort described above (referred to as "cohort 1" of open label extensions), another patient cohort enters an open label extension (referred to as "cohort 3 a"). As with the subjects of cohort 1, the subjects of cohort 3a were PALISADE completors that had been treated with an active agent (i.e., not a placebo) and selected to participate in an open label extension follow-up clinical trial, where subjects were informed that they will continue to receive active treatment. Prior to initiating OLE (exit at PALISADE), the subjects of cohort 3a (self-report) and/or their parents or caregivers/guardians (attorney report) completed the appropriate age of FAQLQ or FAIM, as with the subjects of cohort 1 above. Subjects of cohort 3a additionally received approximately 56 weeks of maintenance therapy comprising administration of 300mg peanut protein per day. At the end of about another 56 weeks of maintenance therapy (i.e., after about 82 weeks total daily 300mg peanut protein maintenance therapy), subjects received a withdrawal double-blind placebo-controlled food challenge. The subjects in cohort 3a and/or their parents/caregivers completed quitting the age-appropriate FAQLQ and FAIM.

31 subjects were assigned to cohort 3a, of which 16 completed withdrawals from FAQLQ and 17 completed withdrawals from FAIM evaluation. As with cohort 1, subjects of cohort 3a had FAQLQ scores that exceeded the developer-reported MID, i.e., total score-0.5 (mean change-0.63, range-1.36, 0.11). In cohort 1, all subdomains exceeded MID, while in cohort 3a, only the emotional impact improved over MID. The FAIM total score exceeded MID for both queues (for queue 1, n-72, average change-0.60, range-0.83 to-0.36; for queue 3a, n-17, average change-0.83, range-1.39 to-0.37). For FAIM, only subjects scored the expected outcome above MID, while in cohort 3a all subdomain FAIM scores improved above MID. These results indicate that, after informing subjects on active therapy, their overall improvement in quality of life is maintained in longer maintenance therapy.

Taken together, these results indicate that peanut OIT can significantly improve the QoL reported by patients across measurement domains. These improvements may be beyond the expectations of the patient's parents/caregivers. Improvement occurs between the initial screening and the initial withdrawal measurements, with the initial withdrawal measurements being taken immediately after first experimental blindness and immediately after the initial desensitization and maintenance period. However, even though significant desensitization was achieved during blind trials, improvements in quality of life continued to manifest during open label extension trials by the blinding method, resulting in even more significant improvements in the overall population.

Example 3 European peanut oral immunotherapy clinical trial

A) And (4) experimental design. The European phase 3 trial (ARTEMIS) was conducted on peanut allergic children who experienced dose limiting symptoms of ≦ 300mg peanut protein (about 1 peanut kernel) during the enrollment double-blind placebo-controlled food challenge (DBPCFC). The trial was a randomized, placebo-controlled, multicenter trial conducted in 18 sites in seven european countries: ireland, France, Germany, Italy, Spain, Sweden and UK.

If children aged 4 to 17 years have a clinical history of peanut allergy, the mean peanut Skin Prick Test (SPT) wheal diameter is 3mm or more and/or the serum peanut-specific immunoglobulin E (psige) level is 0.35kU or more, compared to a negative control_AL (e.g. by

Determined) and experienced a dose limiting symptom of ≦ 300mg peanut protein during the enrollment DBPCFC, then these children were eligible for enrollment. Major exclusion criteria included the occurrence of any severe or life-threatening allergic episodes, severe or uncontrolled asthma, a history of eosinophilic esophagitis, or chronic, recurrent or severe Gastrointestinal (GI) symptoms of undiagnosed etiology within 60 days after screening for DBPCFC.

The eligible subjects were randomized to the active drug (AR 101; investigational biologic drug, including peanut protein) or placebo group at a 3:1 ratio during the initial dose escalation phase of one day, where they were sequentially given doses of 0.5mg to 6mg under the control of the test site. During the 20 to 40 weeks of the dosing phase, subjects received daily doses of peanut protein (AR101) or placebo. The dose was increased weekly until a 300mg dose was reached and maintained for 3 months (initial 3mg to final 300 mg). During the maintenance phase, subjects received a daily dose of 300mg peanut protein for 12 weeks at home. Withdrawal of DBPCFC was performed at the end of the trial visit and challenged with additional 600mg and 1,000mg peanut protein under tolerogenic conditions. The primary endpoint was the proportion of participants who could eat a single dose of 1,000mg peanut protein (about 3 to 4 peanut kernels) in the presence of DBPCFC without dose-limiting symptoms. Additional endpoints include frequency and severity of Adverse Events (AE), and changes in food allergy-related quality of life (QoL).

QoL was assessed using FAQLQ and FAIM measurements. Age-appropriate versions of FAQLQ and FAIM were completed by participants aged 8 to 12 and 13 to 17 years and all caregivers at two time points during the trial: immediately after exiting DBPCFC and blinding, before screening DBPCFC and at the end of visit of the trial. Both tools utilized a seventh scale, where one minute indicated minimal damage, seven indicated maximal damage, and a change of ≧ 0.5 was considered to have exceeded the developer-referenced Minimal Important Difference (MID).

B) And (6) obtaining the result. All primary and secondary endpoints are satisfied. Of the 132 participants receiving active treatment 77 (58.3%) tolerated the 1,000mg peanut protein withdrawal challenge dose, while placebo 1 (2.3%) (treatment difference: 56.0%; 95% CI: 44.1, 65.2; p < 0.0001).

Significant improvements in self-reporting and caregiver-agent reported quality of life assessments were found in participants receiving AR 101. In all FAQLQ domains, improved QoL is self-reported in participants aged 8 to 12 years in the active group. The overall score and the improvement of the "allergen avoidance and diet restriction" and "risk of accidental exposure" domains were statistically significant (the average difference in LS for the activity-placebo was [ 95% CI ]: 1.09[ -1.95, -0.22 ]; -1.18[ -2.06; -0.30; -1.20[ -2.26, -0.15 ]; all p <0.05), respectively).

The degree of improvement in QoL observed for self-reporting and agent reporting varies across all FAIM domains. Participants and caregivers in the active group reported improved scores over MID in the areas of "likelihood of severe reaction" and "probability of death from accidental allergen exposure" and the agents reported improved scores, respectively, compared to the placebo group. The improved scores were surrogate reports and self-reports of the caregiver for the "effective treatment/treatment at accidental exposure" field (LS mean treatment differential-placebo [ 95% Ci ] caregiver self-report from 4 to 12 years of age: 0.85[ -0.17, 1.88] p > 0.05; caregiver surrogate from 4 to 12 years of age: 0.67[ -0.43, 1.77] p > 0.05; caregiver self-report from 13 to 17 years of age: 0.98[0.03, 1.94] p ═ 0.04). The FAQLQ and FAIM results are summarized in fig. 4 to 6.

As expected, active participants experienced more treatment-related adverse events than placebo, which could reduce the quality of life due to exposure to the allergic substance. In view of this expectation, no deterioration in QoL to MID was observed in any of the FAQLQ or FAIM domains in the active group compared to the placebo group.

Claims

1. A method of improving the quality of life of a peanut allergic patient, the method comprising:

administering a peanut composition to the patient according to an oral immunotherapy plan.

2. The method of claim 1, wherein the patient is informed that the peanut composition is being administered.

3. The method of claim 2, wherein the patient is informed that the peanut composition is being administered to the patient at the beginning of the oral immunotherapy plan.

4. The method of claim 2, wherein the patient is informed that the peanut composition is being administered to the patient during a dosing phase of the oral immunotherapy plan.

5. The method of claim 2, wherein the patient is informed that the peanut composition is being administered to the patient during a maintenance phase of the oral immunotherapy plan.

6. The method of claim 1, further comprising informing the patient that the peanut composition is being administered to the patient.

7. The method of claim 6, wherein the patient is informed that the peanut composition is being administered to the patient prior to the start of the oral immunotherapy plan.

8. The method of claim 6, wherein the patient is informed that the peanut composition is being administered to the patient during a dosing phase of an oral immunotherapy plan.

9. The method of claim 6, wherein the patient is informed that the peanut composition is being administered to the patient during a maintenance phase of the oral immunotherapy plan.

10. The method of any one of claims 1-9, wherein the quality of life improvement is measured using a quality of life questionnaire (QoLQ).

11. The method of claim 10, wherein the QoLQ comprises one or more scored measurement domains.

12. The method of claim 11, wherein the QoLQ is a Food Allergy Quality of Life Questionnaire (FAQLQ).

13. The method of claim 12, wherein the FAQLQ is FAQLQ-childhood table (FAQLQ-CF), FAQLQ-junior-years table (FAQLQ-TF), FAQLQ-adult table (FAQLQ-AF), or FAQLQ-father-mother table (FAQLQ-PF).

14. The method of claim 10, wherein the QoLQ is a Food Allergy Independent Measure (FAIM).

15. The method of claim 14, wherein said FAIM is FAIM-childhood table (FAIM-CF), FAIM-minor-year table (FAIM-TF), FAIM-adult table (FAIM-AF), or FAIM-father-mother table (FAIM-PF).

16. A method of improving the quality of life of a peanut allergic patient, as assessed by the quality of life questionnaire (QoLQ), comprising administering a peanut composition to the patient according to an oral immunotherapy plan.

17. The method of claim 16, wherein the patient is informed that the peanut composition is being administered.

18. The method of claim 17, wherein the patient is informed that the peanut composition is being administered to the patient at the beginning of the oral immunotherapy plan.

19. The method of claim 17, wherein the patient is informed that the peanut composition is being administered to the patient during a dosing phase of the oral immunotherapy plan.

20. The method of claim 17, wherein the patient is informed that the peanut composition is being administered to the patient during a maintenance phase of the oral immunotherapy plan.

21. The method of claim 16, further comprising informing the patient that the peanut composition is being administered to the patient.

22. The method of claim 21, wherein the patient is informed that the peanut composition is being administered to the patient prior to the start of the oral immunotherapy plan.

23. The method of claim 21, wherein the patient is informed that the peanut composition is being administered to the patient during a dosing phase of an oral immunotherapy plan.

24. The method of claim 21, wherein the patient is informed that the peanut composition is being administered to the patient during a maintenance phase of the oral immunotherapy plan.

25. The method of any one of claims 16 to 24, wherein the QoLQ comprises one or more scored measurement domains.

26. The method of claim 25, wherein the QoLQ is a Food Allergy Quality of Life Questionnaire (FAQLQ).

27. The method of claim 26, wherein the FAQLQ is FAQLQ-childhood table (FAQLQ-CF), FAQLQ-junior-senior table (FAQLQ-TF), FAQLQ-adult table (FAQLQ-AF), or FAQLQ-father-mother table (FAQLQ-PF).

28. The method of claim 25, wherein the QoLQ is a Food Allergy Independent Measure (FAIM).

29. The method of claim 28, wherein said FAIM is FAIM-childhood table (FAIM-CF), FAIM-minor-year table (FAIM-TF), FAIM-adult table (FAIM-AF), or FAIM-father-mother table (FAIM-PF).

30. The method of claim 25, wherein the QoLQ is a pediatric quality of life manifest (PedsQL).

31. The method of any one of claims 1 to 30, wherein the quality of life is improved for at least 6 months.

32. The method of any one of claims 1 to 31, wherein the quality of life is improved for at least 12 months.

33. A method according to any of claims 11 to 13 or 25 to 27, wherein said one or more score fields of said QoLQ each score on a scale between 1 and 7, or each convert to a score between a first score and a second score, wherein said second score indicates poor quality of life.

34. The method of any one of claims 11 to 13 or 25 to 27, wherein the patient's quality of life is at least a 0.5 point improvement in one or more domains of the QoLQ at a second time point after the period of oral immunotherapy as compared to the assessment at a first time point prior to the period of oral immunotherapy.

35. The method of any one of claims 11 to 17 or 25 to 34, wherein the patient's quality of life is at least a 0.5 point improvement in the total score of QoLQ at a second time point after the period of oral immunotherapy as compared to the assessment at a first time point prior to the period of oral immunotherapy; wherein the total score is an average of the scores of each domain.

36. The method of claim 34 or claim 35, wherein the period of oral immunotherapy between the first and second time points is the dosing phase of the oral immunotherapy plan.

37. The method of claim 34 or claim 35, wherein the period of oral immunotherapy between the first time point and the second time point is at least 1 month of maintenance therapy for which the oral immunotherapy is planned.

38. The method of any one of claims 1-37, wherein the quality of life improves after 6 months of the oral immunotherapy plan.

39. The method of any one of claims 1-38, wherein the oral immunotherapy plan comprises a medicated phase and a maintenance phase.

40. The method of claim 39, wherein the peanut composition is administered to the patient daily during the maintenance phase.

41. The method of claim 39 or claim 40, wherein the maintenance period is at least 3 months.

42. The method of any one of claims 39-41, wherein the peanut composition is administered to the patient at a dose of about 300mg peanut protein or more during a maintenance phase of the oral immunotherapy plan.

43. The method of any one of claims 39 to 42, wherein the medicated phase comprises administering to the patient two or more different doses between about 3mg and the dose of about an initial maintenance phase dose.

44. The method of any one of claims 1-43, wherein the oral immunotherapy plan comprises a dosing phase between about 3 months and about 2 years in length.

45. The method of any one of claims 1-44, wherein the oral immunotherapy plan further comprises an initial escalation phase.

46. The method of any one of claims 1-45, wherein the patient is about 4 years old or older.

47. The method of any one of claims 1 to 46, wherein the patient is between about 4 and about 17 years of age.

48. The method of any one of claims 1 to 47, wherein the patient is between about 8 and about 17 years of age.

49. The method of any one of claims 1 to 48, wherein the method comprises measuring the quality of life prior to administering a peanut composition to the patient according to an oral immunotherapy plan.

50. The method of any one of claims 1 to 49, wherein the method comprises measuring the quality of life after administering a peanut composition to the patient according to an oral immunotherapy plan.

51. The method of any one of claims 2 to 15 or 17 to 50, wherein the method comprises measuring the quality of life after informing the patient that the peanut composition is being administered.

52. The method of any one of claims 1-51, wherein the quality of life of the patient is improved as determined by a quality of life questionnaire (QoLQ).